WO2026010899A1 - Methods of deteriming and predicting the effectiveness of immune checkpoint inhibitor treatment in subjects with hepatocellular carcinoma - Google Patents

Abstract

Provided herein are methods and systems to determine whether immune checkpoint inhibitor (ICI) treatment is likely to be effective in subjects suspected of or suffering from hepatocellular carcinoma (HCC). The methods and systems described herein utilize the concentration of laminin γ2 monomer (LG2m) in a biological sample obtained from a subject to assess or predict whether ICI treatment will be or is likely to be effective in said subject.

Description

Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 METHODS OF DETERIMING AND PREDICTING THE EFFECTIVENESS OF IMMUNE CHECKPOINT INHIBITOR TREATMENT IN SUBJECTS WITH HEPATOCELLULAR CARCINOMA RELATED APPLICATION INFORMATION This application claims priority to U.S. Application No.63/666,794, filed on July 2, 2024, the contents of which are herein incorporated by reference. TECHNICAL FIELD The present disclosure relates to methods and systems to determine whether immune checkpoint inhibitor (ICI) treatment is likely to be effective in subjects suspected of or suffering from hepatocellular carcinoma (HCC). In particular, the methods and systems utilize the concentration of laminin γ2 monomer (LG2m) in a biological sample obtained from a subject to assess or predict whether ICI treatment will be or is likely to be effective in said subject. BACKGROUND Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, characterized by the malignant transformation of hepatocytes, the main cells of the liver. It typically arises in the setting of chronic liver disease and cirrhosis, often as a result of viral hepatitis infection (such as hepatitis B or C), alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), or other underlying liver conditions. This malignancy imposes a substantial global health burden, with an estimated annual incidence surpassing 40,000 new cases in the United States alone. Despite advancements in diagnostic and therapeutic approaches, the prognosis for patients with HCC remains poor, primarily due to challenges in early detection, limited treatment options, and high rates of recurrence following treatment. Treatment strategies for HCC center upon the tumor stage and the patient's overall health status. In early-stage HCC, certain patients may find benefit in curative interventions like liver transplant, surgical resection, and radiofrequency ablation. Conversely, for those with intermediate or advanced-stage disease, options may include transcatheter arterial chemoembolization (TACE), radioembolization, systemic targeted agents, and radiation therapy. Immune checkpoint inhibition (ICI) treatment, in particular, has revolutionized cancer therapy, extending its reach to hepatocellular carcinoma, which accounts for 80%-90% of liver cancer cases and ranks as the third most common cause of cancer-related deaths worldwide. Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 However, a prevalent challenge across these treatment modalities, particularly with ICI, is the unpredictability of therapeutic response. Variations in the HCC immune microenvironment among individuals can profoundly influence treatment efficacy. Consequently, issues such as wasted time for patients and significant financial strain on healthcare systems arise, especially considering the high cost of these medications. Thus, there arises a critical need for preemptive and/or monitoring tools to aid in evaluating treatment efficacy before, during, and after the course of a patient’s HCC treatment journey. SUMMARY OF THE INVENTION Provided herein are methods and systems for determining and predicting the status of the immunosuppressive system of the cancer microenvironment in a subject. In particular, methods and systems are provided that employ a subject’s laminin γ2 monomer (LG2m) concentration to assess, determine and aid in risk classification of the effectiveness of immune checkpoint inhibitor (ICI) treatment and hepatocellular carcinoma (HCC) status. Further provided herein are methods for determining whether a subject suffering from or suspected of suffering from hepatocellular carcinoma (HCC) should be administered at least one immune checkpoint inhibitor, the method comprising the steps of: (a) obtaining a biological sample from a subject suffering from or suspected of suffering from HCC; (b) determining the concentration of laminin γ2 monomer (LG2m) in the biological sample; and (c) administering at least one immune checkpoint inhibitor to the subject if the LG2m concentration from the biological sample is lower than a reference level or not administering at least one immune checkpoint inhibitor to the subject if the LG2m concentration from the biological sample is higher than a reference level. Also provided herein are methods for predicting whether a subject suffering from or suspected of suffering from hepatocellular carcinoma (HCC) is likely to respond to treatment with at least one immune checkpoint inhibitor, the method comprising the steps of: (a) obtaining a biological sample from a subject suffering from or suspected of suffering from HCC; (b) determining the concentration of laminin γ2 monomer (LG2m) in the biological sample; and (c) predicting that the subject is likely: (i) to respond to treatment with at least one immune checkpoint inhibitor if the LG2m concentration from the biological sample is lower than a reference level; or (ii) not to respond to treatment with at least one immune checkpoint inhibitor if the LG2m concentration form the biological sample is higher than a reference level. Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 In some embodiments, the method further comprises administering at least one immune checkpoint inhibitor to the subject predicted as likely to respond to treatment with at least one immune checkpoint inhibitor. In some embodiments, the biological sample is a plasma sample or a serum sample. In other embodiments, the biological sample is a serum sample. In some embodiments, the concentration of LG2m in the biological sample is determined by an immunoassay, a clinical chemistry assay, a single molecule detection assay, cytometry, or any combinations thereof. In further embodiments, the concentration of LG2m in the biological sample is determined by an immunoassay. In other embodiments, the reference level is about 10 pg/mL, about 15 pg/mL, about 20 pg/mL, about 25 pg/mL, about 30 pg/mL, about 35 pg/mL, about 40 pg/mL, about 45 pg/mL, about 50 pg/mL, about 55 pg/mL, about 60 pg/mL, about 65 pg/mL, about 70 pg/mL or about 75 pg/mL, about 80 pg/mL, about 85 pg/mL, about 90 pg/mL, about 95 pg/mL or about 100 pg/mL. In some embodiments, at least one immune checkpoint inhibitor is atezolizumab, avelumab, cemiplimab, dostarlimab, ipilimumab, nivolumab, pembrolizumab, retifanlimab, toripalimab, tremelimumab, durvalumab or any combinations thereof. In some embodiments, the at least one immune checkpoint inhibitor is administered in combination with a second therapeutic agent. In some embodiments, the second therapeutic agent is at least one anti-angiogenesis drug. In further embodiments, the at least one anti-angiogenesis drug is bevacizumab. In some embodiments of the above method, the subject is a human. Provided here are methods for monitoring a subject suffering from hepatocellular carcinoma (HCC) and receiving treatment with at least one immune checkpoint inhibitor, the method comprising the steps of: (a) obtaining a biological sample from a subject suffering from HCC and receiving treatment with at least one immune checkpoint inhibitor; (b) determining the concentration of laminin γ2 monomer (LG2m) in the biological sample; and (c) continuing to treat the subject with the at least one immune checkpoint inhibitor if the LG2m concentration from the biological sample is lower than a reference level or discontinuing treatment with the at least one immune checkpoint inhibitor if the LG2m concentration from the biological sample is higher than a reference level. In some embodiments, the biological sample is a plasma sample or a serum sample. In further embodiments, the biological sample is a serum sample. In other embodiments, the concentration of LG2m in the biological sample is determined by an immunoassay, a clinical Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 chemistry assay, a single molecule detection assay, cytometry, or any combinations thereof. In further embodiments, the concentration of LG2m in the biological sample is determined by an immunoassay. In some embodiments, the reference level is about 10 pg/mL, about 15 pg/mL, about 20 pg/mL, about 25 pg/mL, about 30 pg/mL, about 35 pg/mL, about 40 pg/mL, about 45 pg/mL, about 50 pg/mL, about 55 pg/mL, about 60 pg/mL, about 65 pg/mL, about 70 pg/mL or about 75 pg/mL, about 80 pg/mL, about 85 pg/mL, about 90 pg/mL, about 95 pg/mL or about 100 pg/mL. In some embodiments, the at least one immune checkpoint inhibitor is atezolizumab, avelumab, cemiplimab, dostarlimab, ipilimumab, nivolumab, pembrolizumab, retifanlimab, toripalimab, tremelimumab, durvalumab or any combinations thereof. In some embodiments of the above method, the subject is a human. BRIEF DESCRIPTION OF THE DRAWINGS Having thus described the presently disclosed subject matter in general terms, reference will now be made to the accompanying Figures, which are not necessarily drawn to scale, and wherein: FIGURE 1 shows a dot plot indicating the relationship between serum LG2m concentration and T-cell infiltration in FIG. 1A. FIG. 1B shows a schematic representation of the T cell infiltration at the tumor peripheral area in resected liver cancer tissues with serum low (< 50 pg/ml) and high (≥ 50 pg/ml) LG2m, respectively. FIGURE 2 shows single-cell spatial analysis by CODEX tumor infiltration of T cells is low in FIG. 2A (< 50 pg/ml) and high in FIG. 2B (≥ 50 pg/ml) in LG2m serum at the tumor peripheral area in resected liver cancer tissues. FIGURE 3 shows cell neighborhood analysis indicting cellular diversity in LG2m low (< 50 pg/ml) populations (FIG.3A) and LG2m high (≥ 50 pg/ml) populations (FIG.3B). FIGURE 4 shows the results of single-cell spatial analysis by CODEX in CTL (FIG 4A), Th cells (FIG.4B), macrophage and endothelial cells (EC cells) (FIG.4C), cancer stem cells (CSC) (FIG.4D), B cell and stromal cells and the markers used for spatial single-cell analysis CODEX (FIG.4E) Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 FIGURE 5 shows progression-free survival (PFS) by Kaplan-Meier analysis in (A) all patients (FIG.5A), LG2m low patients (serum LG2m < 49.3 pg/mL) (FIG.5B), and LG2m high patients (serum LG2m ≥ 49.3 pg/mL) (FIG.5C). FIG.6 shows the overall Survival (OS) by Kaplan-Meier analysis in all patients (FIG.6A), LG2m low patients (serum LG2m < 49.3 pg/mL) (FIG. 5B), and LG2m high patients (serum LG2m ≥ 49.3 pg/mL) (FIG.6C). DETAILED DESCRIPTION Measuring LG2m in biological samples obtained from a subject can serve as a predictive tool for assessing the immune microenvironment in hepatocellular carcinoma (HCC). While various immune checkpoint inhibitors (ICIs) are available for HCC treatment, the lack of reliable biomarkers to forecast their therapeutic effects leads to a post-administration evaluation approach. This often results in significant delays for patients and imposes substantial financial strains on healthcare systems due to the high cost of these medications. Leveraging LG2m levels in biological samples, such as in serum samples, offers a straightforward and non-invasive means to anticipate the efficacy of ICIs, aiding in the proactive selection of treatment strategies. By incorporating LG2m assessment into clinical practice, healthcare providers can streamline decision-making processes, optimize treatment plans, and potentially reduce the burden on patients and healthcare budgets. DEFINITIONS The terms "comprise(s)," "include(s)," "having," "has," "can," "contain(s)," and variants thereof, as used herein, are intended to be open-ended transitional phrases, terms, or words that do not preclude the possibility of additional acts or structures. The singular forms "a," "and," and "the" include plural references unless the context clearly dictates otherwise. The present disclosure also contemplates other embodiments "comprising," "consisting of," and "consisting essentially of," the embodiments or elements presented herein, whether explicitly set forth or not. For the recitation of numeric ranges herein, each intervening number there between with the same degree of precision is explicitly contemplated. For example, for the range of 6-9, the numbers 7 and 8 are contemplated in addition to 6 and 9, and for the range 6.0-7.0, the number 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, and 7.0 are explicitly contemplated. Unless otherwise defined herein, scientific, and technical terms used in connection with the present disclosure shall have the meanings that are commonly understood by those of ordinary skill in the art. The meaning Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 and scope of the terms should be clear; in the event, however of any latent ambiguity, definitions provided herein take precedent over any dictionary or extrinsic definition. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. The terms "or" means "and/or" unless stated otherwise. Furthermore, the use of the terms "including" and "having," as well as other forms of those terms, such as "includes," "included", "has," and "have" are not limiting. The term "about" is utilized herein to specify precise numerical support for the value it precedes, as well as to encompass numbers in close proximity to or approximating the specified value. Certain ranges are delineated in this document with numerical values preceded by the term "about." When determining if a number is near to or approximates a specifically stated value, the unrecited number that closely approximates the stated value, considering the context in which it is presented, may be deemed substantially equivalent to the specified number. In instances where a range of values is provided, it is understood that every value within that range, to the nearest tenth of the unit of the lower limit unless otherwise indicated by the context, including any other stated or intervening values within that range, falls within the scope of the invention. Both the upper and lower limits of these smaller ranges may be included independently within the smaller ranges and are also considered part of the invention, except where explicitly excluded by stated limits within the range. If the stated range includes one or both of its limits, ranges excluding either or both of these included limits are also considered part of the invention. The term "control" as used herein when referring to a composition, can refer to a composition known to not contain an analyte of interest ("negative"), e.g., laminin gamma 2 monomer (laminin gamma 2 monomer or variants of laminin gamma 2 monomer, or combinations thereof); or to contain an analyte of interest ("positive control"), e.g., laminin gamma 2 monomer (such as human laminin gamma 2 monomer, variants of laminin gamma 2 monomer, or any combinations thereof). A positive control can comprise a known concentration of laminin gamma 2 monomer. "Control," "positive control," and "calibrator" may be used interchangeably herein to refer to a composition comprising a known concentration of laminin gamma 2 monomer. A "positive control" can be used to establish assay performance characteristics and is a useful indicator of the integrity of reagents (e.g., analytes). A "normal control" or "healthy control" may Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 refer to a sample or specimen taken from a subject, or an actual subject who does not have cancer, or is not at risk of developing cancer. As used herein, the term "laminin gamma-2 monomer," "laminin-5 gamma-2 monomer," "LN-5 gamma-2 monomer," "gamma-2 monomer," "gamma-2," "g-2 monomer" or any of the preceding terms with the "γ" symbol in place of the word "gamma" or the letter "g" are all interchangeable and refer to one of the polypeptide chains that constitutes laminin-5 (also known as "kalinin" and "nicein" among other synonyms) and is identified as the gamma (γ) chain (as opposed to the alpha (α) and beta (β) chains), of the gamma-2 molecular species (contrasting from the gamma-1 species). In some embodiments laminin gamma-2 monomer can relate to any laminin gamma-2 monomer sequence, including an amino acid sequence (e.g., protein, polypeptide, peptide (precursor or mature), fusions, derivatives, variants, etc. or a nucleic acid sequence encoding such an amino acid sequence (e.g., DNA or RNA fragments, truncations, fusions, derivatives, SNPs, variants, etc.). Laminin gamma-2 monomer can be from any organism and, in some embodiments, comprises an amino acid sequence from higher eukaryotes, including mammals. In some non-limiting embodiments a laminin gamma-2 monomer can be selected from any of human (including isoforms a and b, UniProtKB/Swiss-Prot: Q13753; RefSeq NP_005553.2), mouse (M musculus, UniProt: E9Q7G3; RefSeq NP_032511.3), rat (R. norvegicus, GenBank: NP 001094110 (precursor protein); UniProtKB/TrEMBL: F1LRH4) and chicken (G. gallus, GenBank AAS92197; UniProtKB/TrEMBL Q6PVZ6 (partial sequences)), as well as fly and worm. In some embodiments, laminin gamma-2 monomer comprises human laminin-5 gamma- 2 monomer (encoded by GenBank accession no. NM_005562 (mRNA), or the amino acid sequence associated with UniProtKB accession no. Q13753). In humans, the gene for laminin gamma-2 monomer (or "LAMC2") is located on the q arm of chromosome 1 (1q25.3). Human laminin gamma-2 monomer sequences can include the precursor protein sequence that includes a signal peptide (usually amino acids 1-21) that is cleaved off to generate the mature secreted protein (amino acids 22-1193). Laminin gamma-2 monomer can also encompass any fusion protein as well as any amino acid sequence variants. As noted above, laminin gamma-2 monomer is unique to laminin 5 which is predominantly localized in basil lamina and basement membrane. As used herein, the term "cancer" refers to any malignant disease associated with unregulated cell proliferation, growth, invasion, and metastasis, or mass (e.g., angiogenic, Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 neoplastic, or tumorigenic cell growth). In some embodiments, cancer can comprise hepatocellular carcinoma (HCC). Hepatocellular carcinoma (HCC) typically arises from hepatocytes, the main cells of the liver. It is classified based on various factors including tumor size, number of nodules, and presence of vascular invasion. Large nodules with well-defined borders are often termed as solitary lesions, while multifocal HCC presents with multiple tumor nodules. Vascular invasion, particularly involving the portal vein, is associated with a more aggressive disease course and poorer prognosis. Several risk factors contribute to the development of HCC. Chronic viral hepatitis infections, notably hepatitis B virus (HBV) and hepatitis C virus (HCV), are major etiological factors worldwide. Other risk factors include chronic alcohol consumption, non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH), exposure to aflatoxin B1, cirrhosis, and genetic predisposition such as hereditary hemochromatosis and alpha-1 antitrypsin deficiency. Additionally, certain environmental toxins and carcinogens, such as aflatoxin exposure from contaminated food, may increase the risk of HCC development. Hepatocellular carcinoma (HCC) is typically associated with a variety of symptoms, including abdominal pain, jaundice, weight loss, fatigue, loss of appetite, nausea, and vomiting. Diagnostic tests commonly used for detecting HCC include liver ultrasound, CT scan, MRI, alpha- fetoprotein (AFP) blood test, liver biopsy, and sometimes angiography. Staging of HCC is crucial for determining prognosis and treatment options, with stages ranging from 0 to IV. Stage 0 involves very early tumors, while Stage IV indicates advanced disease with metastasis to distant organs such as the lungs or bones. When HCC metastasizes, it often spreads to nearby organs such as the lungs, bones, lymph nodes, or abdominal organs like the pancreas. The prognosis and treatment approach for HCC depend largely on the stage of the disease at diagnosis and the overall health of the patient. “Reference level” as used herein refers to an assay cutoff value that is used to assess diagnostic, prognostic, or therapeutic efficacy and that has been linked or is associated herein with various clinical parameters (e.g., presence of disease, stage of disease, severity of disease, progression, non-progression, or improvement of disease, etc.). This disclosure provides exemplary reference levels. However, it is well-known that reference levels may vary depending on the nature of the immunoassay (e.g., antibodies employed, reaction conditions, sample purity, Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 etc.) and that assays can be compared and standardized. It further is well within the ordinary skill of one in the art to adapt the disclosure herein for other immunoassays to obtain immunoassay- specific reference levels for those other immunoassays based on the description provided by this disclosure. Whereas the precise value of the reference level may vary between assays, the findings as described herein should be generally applicable and capable of being extrapolated to other assays. In certain embodiments described herein, the reference level is described as determined by any assay having a certain specificity and sensitivity. As used herein, the term "antibody" refers to an immunoglobulin molecule or immunologically active portion thereof, namely, an antigen-binding portion. Examples of immunologically active portions of immunoglobulin molecules include F(ab) and F(ab')2 fragments which can be generated by treating an antibody with an enzyme, such as pepsin. Examples of antibodies that can be used in the present disclosure include, but are not limited to, antiserum, polyclonal antibodies, monoclonal antibodies, chimeric antibodies, human antibodies, humanized antibodies, recombinant antibodies, single-chain Fvs ("scFv"), an affinity maturated antibody, single chain antibodies, single domain antibodies, F(ab) fragments, F(ab') fragments, disulfide-linked Fvs ("sdFv"), and anti-idiotypic ("anti-Id") antibodies and functionally active epitope-binding fragments of any of the above. “Label” and “detectable label” as used herein refer to a moiety attached to an antibody or an analyte to render the reaction between the antibody and the analyte detectable, and the antibody or analyte so labeled is referred to as “detectably labeled.” A label can produce a signal that is detectable by visual or instrumental means. Various labels include signal-producing substances, such as chromagens, fluorescent compounds, chemiluminescent compounds, radioactive compounds, and the like. Representative examples of labels include moieties that produce light, e.g., acridinium compounds, and moieties that produce fluorescence, e.g., fluorescein. Other labels are described herein. In this regard, the moiety itself may not be detectable but may become detectable upon reaction with yet another moiety. Use of the term “detectably labeled” is intended to encompass such labeling. Any suitable detectable label as is known in the art can be used. For example, the detectable label can be a radioactive label (such as 3H, 14C, 32P, 33P, 35S, 90Y, 99Tc, 111In, 125I, 131I, 177Lu, 166Ho, and 153Sm), an enzymatic label (such as horseradish peroxidase, alkaline peroxidase, glucose 6-phosphate dehydrogenase, and the like), a chemiluminescent label Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 (such as acridinium esters, thioesters, or sulfonamides; luminol, isoluminol, phenanthridinium esters, and the like), a fluorescent label (such as fluorescein (e.g., 5-fluorescein, 6- carboxyfluorescein, 3’6-carboxyfluorescein, 5(6)-carboxyfluorescein, 6-hexachloro-fluorescein, 6-tetrachlorofluorescein, fluorescein isothiocyanate, and the like)), rhodamine, phycobiliproteins, R-phycoerythrin, quantum dots (e.g., zinc sulfide-capped cadmium selenide), a thermometric label, or an immuno-polymerase chain reaction label. An introduction to labels, labeling procedures and detection of labels is found in Polak and Van Noorden, Introduction to Immunocytochemistry, 2nd ed., Springer Verlag, N.Y. (1997), and in Haugland, Handbook of Fluorescent Probes and Research Chemicals (1996), which is a combined handbook and catalogue published by Molecular Probes, Inc., Eugene, Oregon. A fluorescent label can be used in FPIA (see, e.g., U.S. Patent Nos.5,593,896, 5,573,904, 5,496,925, 5,359,093, and 5,352,803, which are hereby incorporated by reference in their entireties). An acridinium compound can be used as a detectable label in a homogeneous chemiluminescent assay (see, e.g., Adamczyk et al., Bioorg. Med. Chem. Lett.16: 1324-1328 (2006); Adamczyk et al., Bioorg. Med. Chem. Lett.4: 2313-2317 (2004); Adamczyk et al., Biorg. Med. Chem. Lett.14: 3917-3921 (2004); and Adamczyk et al., Org. Lett.5: 3779-3782 (2003)). In one embodiment, the acridinium compound is an acridinium-9-carboxamide. Methods for preparing acridinium 9-carboxamides are described in Mattingly, J. Biolumin. Chemilumin.6: 107-114 (1991); Adamczyk et al., J. Org. Chem.63: 5636-5639 (1998); Adamczyk et al., Tetrahedron 55: 10899-10914 (1999); Adamczyk et al., Org. Lett.1: 779-781 (1999); Adamczyk et al., Bioconjugate Chem.11: 714-724 (2000); Mattingly et al., In Luminescence Biotechnology: Instruments and Applications; Dyke, K. V. Ed.; CRC Press: Boca Raton, pp.77–105 (2002); Adamczyk et al., Org. Lett.5: 3779-3782 (2003); and U.S. Patent Nos.5,468,646, 5,543,524 and 5,783,699 (each of which is incorporated herein by reference in its entirety for its teachings regarding same). Another example of an acridinium compound is an acridinium-9-carboxylate aryl ester. An example of an acridinium-9-carboxylate aryl ester of formula II is 10-methyl-9- (phenoxycarbonyl)acridinium fluorosulfonate (available from Cayman Chemical, Ann Arbor, MI). Methods for preparing acridinium 9-carboxylate aryl esters are described in McCapra et al., Photochem. Photobiol., 4: 1111-21 (1965); Razavi et al., Luminescence 15: 245-249 (2000); Razavi et al., Luminescence 15: 239-244 (2000); and U.S. Patent No.5,241,070 (each of which Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 is incorporated herein by reference in its entirety for its teachings regarding same). Such acridinium-9-carboxylate aryl esters are efficient chemiluminescent indicators for hydrogen peroxide produced in the oxidation of an analyte by at least one oxidase in terms of the intensity of the signal and/or the rapidity of the signal. The course of the chemiluminescent emission for the acridinium-9-carboxylate aryl ester is completed rapidly, i.e., in under 1 second, while the acridinium-9-carboxamide chemiluminescent emission extends over 2 seconds. Acridinium-9- carboxylate aryl ester, however, loses its chemiluminescent properties in the presence of protein. Therefore, its use requires the absence of protein during signal generation and detection. Methods for separating or removing proteins in the sample are well-known to those skilled in the art and include, but are not limited to, ultrafiltration, extraction, precipitation, dialysis, chromatography, and/or digestion (see, e.g., Wells, High Throughput Bioanalytical Sample Preparation. Methods and Automation Strategies, Elsevier (2003)). The amount of protein removed or separated from the test sample can be about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, or about 95%. Further details regarding acridinium-9-carboxylate aryl ester and its use are set forth in U.S. Patent App. No.11/697,835, filed April 9, 2007. Acridinium-9-carboxylate aryl esters can be dissolved in any suitable solvent, such as degassed anhydrous N,N-dimethylformamide (DMF) or aqueous sodium cholate. As used herein, the term “microparticle(s)” refers to small particles with dimensions typically ranging from 0.1 to 100 micrometers (μm). These particles can be solid or colloidal in nature. Microparticles can include, but are not limited to, polymeric microparticles, liposomes, microspheres, nanoparticles, magnetic microparticles, non-magnetic microparticles, protein microparticles, biodegradable microparticles, ceramic microparticles, hollow microparticles, Janus particles, nanospheres, microcapsules, and nanocapsules. In some cases, microparticle can include one or more of the following: a poly (lactide-co-glycolide), aliphatic polyesters including, but not limited to, poly-glycolic acid and poly-lactic acid, hyaluronic acid, modified polysaccharides, chitosan, cellulose, dextran, polyurethanes, polyacrylic acids, pseudo- poly(amino acids), polyhydroxybutyrate-related copolymers, polyanhydrides, polymethylmethacrylate, poly(ethylene oxide), lecithin and phospholipids, in any combination thereof. Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 “Non-point-of-care device” refers to a device that is not a point-of-care device or a single use device. A non-point-of-care device refers to any device that does not meet any of the above limitations of a point-of-care or a single use device as defined herein. In some embodiments, the non-point-of-care device may be a relatively large instrument, such as a tabletop instrument. Accordingly, in some embodiments the non-point-of-care device is not a handheld instrument. In some embodiments, the non-point-of-care device is capable of performing an assay on more than one clinical sample simultaneously. Suitable non-point-of-care devices include, for example, the Architect or Alinity platforms produced by Abbott Core Laboratories. “Point-of-care device” refers to a device used to provide medical diagnostic testing at or near the point-of-care (namely, outside of a laboratory), at the time and place of patient care (such as in a hospital, physician’s office, urgent or other medical care facility, a patient’s home, a nursing home and/or a long-term care and/or hospice facility). Examples of point-of-care devices include those produced by Abbott Laboratories (Abbott Park, IL) (e.g., i-STAT and i- STAT Alinity, Universal Biosensors (Rowville, Australia) (see US 2006/0134713), Axis-Shield PoC AS (Oslo, Norway) and Clinical Lab Products (Los Angeles, USA). In some embodiments, the point-of-care device is a single-use device. The term “single-use device” or “single-use instrument” refers to a clinical diagnostic instrument that processes and performs a clinical diagnostic assay on a unit use basis (such as, for example, a single-use cartridge) for a single patient sample. A point-of-care instrument does not perform an assay on more than one clinical sample simultaneously. However, the point-of-care instrument may have the capability to measure more than one parameter (e.g., more than one analyte) in an individual clinical sample per unit use basis. “Recombinant antibody” and “recombinant antibodies” refer to antibodies prepared by one or more steps, including cloning nucleic acid sequences encoding all or a part of one or more monoclonal antibodies into an appropriate expression vector by recombinant techniques and subsequently expressing the antibody in an appropriate host cell. The terms include, but are not limited to, recombinantly produced monoclonal antibodies, chimeric antibodies, humanized antibodies (fully or partially humanized), multi-specific or multi-valent structures formed from antibody fragments, bifunctional antibodies, heteroconjugate Abs, DVD-Ig®s, and other antibodies as described in (i) herein. (Dual-variable domain immunoglobulins and methods for Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 making them are described in Wu, C., et al., Nature Biotechnology, 25:1290-1297 (2007)). The term “bifunctional antibody,” as used herein, refers to an antibody that comprises a first arm having a specificity for one antigenic site and a second arm having a specificity for a different antigenic site, i.e., the bifunctional antibodies have a dual specificity. “Reference level” as used herein refers to an assay cutoff value that is used to assess diagnostic, prognostic, or therapeutic efficacy and that has been linked or is associated herein with various clinical parameters (e.g., presence of disease, stage of disease, severity of disease, progression, non-progression, or improvement of disease, etc.). This disclosure provides exemplary reference levels. However, it is well-known that reference levels may vary depending on the nature of the immunoassay (e.g., antibodies employed, reaction conditions, sample purity, etc.) and that assays can be compared and standardized. It further is well within the ordinary skill of one in the art to adapt the disclosure herein for other immunoassays to obtain immunoassay- specific reference levels for those other immunoassays based on the description provided by this disclosure. Whereas the precise value of the reference level may vary between assays, the findings as described herein should be generally applicable and capable of being extrapolated to other assays. In certain embodiments described herein, the reference level is described as being determined by any assay having a certain specificity and sensitivity. “Sample,” “test sample,” “specimen,” “sample from a subject,” “biological sample,” and “patient sample” as used interchangeably herein may be a sample of blood, such as whole blood (including for example, capillary blood, venous blood, dried blood spot, etc.), serum or plasma, or tissue, saliva, urine, amniotic fluid, an oropharyngeal specimen, a nasopharyngeal specimens, lower respiratory specimens such as, but not limited to, sputum, endotracheal aspirate or bronchoalveolar lavage, cerebrospinal fluid, placental cells or tissue, endothelial cells, leukocytes, or monocytes. The sample can be used directly as obtained from a patient or can be pre-treated, such as by filtration, distillation, extraction, concentration, centrifugation, inactivation of interfering components, addition of reagents, and the like, to modify the character of the sample in some manner as discussed herein or otherwise as is known in the art. Additionally, the sample can be a nasopharyngeal or oropharyngeal sample obtained using one or more swabs that, once obtained, is placed in a sterile tube containing a virus transport media (VTM) or universal transport media (UTM) and retained therein or transferred to another media for testing. Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 A variety of cell types, tissue, or bodily fluid may be utilized to obtain a sample. Such cell types, tissues, and fluid may include sections of tissues such as biopsy and autopsy samples, oropharyngeal specimens, nasopharyngeal specimens, frozen sections taken for histologic purposes, blood (such as whole blood, dried blood spots, etc.), plasma, serum, saliva, red blood cells, platelets, interstitial fluid, cerebral spinal fluid, etc. Cell types and tissues may also include lymph fluid, cerebrospinal fluid, or any fluid collected by aspiration. A tissue or cell type may be provided by removing a sample of cells from a human and a non-human animal but can also be accomplished by using previously isolated cells (e.g., isolated by another person, at another time, and/or for another purpose). Archival tissues, such as those having treatment or outcome history, may also be used. Protein or nucleotide isolation and/or purification may not be necessary. In some embodiments, the sample is a blood sample (e.g., a whole blood sample, a serum sample, or a plasma sample). In some embodiments, the sample is a whole blood sample. In some embodiments, the sample is a capillary blood sample. In some embodiments, the sample is a dried blood spot. In some embodiments, the sample is a serum sample. In yet another embodiment, the sample is a plasma sample. In some embodiments, the sample is an oropharyngeal specimen. In other embodiments, the sample is a nasopharyngeal specimen. In other embodiments, the sample is spectrum. In other embodiments, the sample is endotracheal aspirate. In still yet other embodiments, the sample is bronchoalveolar lavage. In still yet other embodiments, the sample is a saliva sample. “Specific binding” or “specifically binding” as used herein may refer to the interaction of an antibody, a protein, or a peptide with a second chemical species, wherein the interaction is dependent upon the presence of a particular structure (e.g., an antigenic determinant or epitope) on the chemical species; for example, an antibody recognizes and binds to a specific protein structure rather than to proteins generally. If an antibody is specific for epitope “A”, the presence of a molecule containing epitope A (or free, unlabeled A), in a reaction containing labeled “A” and the antibody, will reduce the amount of labeled A bound to the antibody. “Specific binding partner” is a member of a specific binding pair. A specific binding pair comprises two different molecules, which specifically bind to each other through chemical or physical means. Therefore, in addition to antigen and antibody specific binding pairs of common immunoassays, other specific binding pairs can include biotin and avidin (or streptavidin), carbohydrates and lectins, complementary nucleotide sequences, effector and receptor molecules, Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 cofactors and enzymes, enzymes and enzyme inhibitors, and the like. Furthermore, specific binding pairs can include members that are analogs of the original specific binding members, for example, an analyte-analog. Immunoreactive specific binding members include antigens, antigen fragments, and antibodies, including monoclonal and polyclonal antibodies as well as complexes and fragments thereof, whether isolated or recombinantly produced, and aptamers. “Subject” and “patient” as used herein interchangeably refers to any vertebrate, including, but not limited to, a mammal (e.g., cow, pig, camel, llama, horse, goat, rabbit, sheep, hamsters, guinea pig, cat, dog, rat, and mouse, a non-human primate (for example, a monkey, such as a cynomolgus or rhesus monkey, chimpanzee, etc.) and a human). In some embodiments, the subject may be a human or a non-human. In some embodiments, the subject is a human. The subject or patient may be undergoing other forms of treatment. In some embodiments, the subject may be a human or a non-human. In some embodiments, the subject may be a human patient at risk for developing or already having cancer such as, for example, liver cancer or HCC. “Treat,” “treating” or “treatment” are each used interchangeably herein to describe reversing, alleviating, or inhibiting the progress of a disease or one or more symptoms of such disease, to which such term applies. In some aspects, a treatment may be either performed in an acute or chronic way. Depending on the condition of the subject, the term also refers to preventing a disease and includes preventing the onset of a disease, or preventing the symptoms associated with a disease. "Preventing" also refers to preventing the recurrence of a disease or of one or more symptoms associated with such disease. "Treatment" and "therapeutically," refer to the act of treating, as "treating" is defined above. In some aspects, the prevention or treatment of a disease can be done prior to affliction or injury, such as, for example, to reduce the severity of a disease or symptoms associated with a disease. Such prevention or reduction can include (a) administration of one or more pharmaceutical composition and/or one or more nutritional compositions to a subject; (b) the use of one or more surgical interventions (e.g., angioplasty, inserting a stent, atherectomy, bypass surgery or any combinations thereof); or (c) any combinations of (a) and (b). Methods well-known in the art for collecting, handling and processing urine, blood, serum and plasma, and other body fluids, are used in the practice of the present disclosure, for instance, when the antibodies provided herein are employed as immunodiagnostic reagents, and/or in laminin gamma-2 monomer immunoassay kit. The test sample can comprise further moieties in addition to the analyte of interest, such as antibodies, antigens, haptens, hormones, drugs, enzymes, Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 receptors, proteins, peptides, polypeptides, oligonucleotides or polynucleotides. For example, the sample can be a whole blood sample obtained from a subject. It can be necessary or desired that a test sample, particularly whole blood, be treated prior to immunoassay as described herein, e.g., with a pretreatment reagent. Even in cases where pretreatment is not necessary (e.g., most urine samples, a pre-processed archived sample, etc.), pretreatment of the sample is an option that can be performed for mere convenience (e.g., as part of a protocol on a commercial platform). The sample may be used directly as obtained from the subject or following pretreatment to modify a characteristic of the sample. Pretreatment may include extraction, concentration, inactivation of interfering components, and/or the addition of reagents. _{1. Use o f Lamin in Gamm a -2 m onom er for Predic t ing the Cancer Microenv ironm ent} Provided herein are methods and systems for determining and predicting the immunosuppressive system of the cancer microenvironment in a subject. In some embodiments, the subject is a mammal. In other embodiments, the subject is a human. In particular, methods and systems are provided that employ a subject’s laminin γ2 monomer (LG2m) concentration (e.g., level or amount) obtained from a biological sample to assess whether a subject suffering from or suspected of suffering from hepatocellular carcinoma (HCC) should be administered at least one immune checkpoint inhibitor, predicting whether a subject suffering from or suspected of suffering from HCC is likely to respond to treatment with at least one immune checkpoint inhibitor, and monitoring subjects suffering from HCC and receiving treatment with at least one immune checkpoint inhibitor. The LG2m measured in the methods described herein can include fragments thereof, degradation products thereof, and/or enzymatic cleavage products thereof. In some embodiments, the methods involve assessing or determining whether a subject suffering from or suspected of suffering from HCC should be treated with at least one immune checkpoint inhibitor. In one embodiment, the method comprises at least the steps of: (a) obtaining a biological sample from a subject suffering from or suspected of suffering from HCC; (b) determining the concentration of LG2m in the biological sample; and (c) administering at least one immune checkpoint inhibitor to the subject if the LG2m concentration from the biological sample is lower than a reference level or not administering at least one immune checkpoint inhibitor to the subject if the LG2m concentration from the biological sample is higher than a reference level. Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 In yet another embodiment, also provided herein are methods for predicting whether a subject (e.g., a mammal, such as a human) suffering from or suspected of suffering from HCC is likely to respond to treatment with at least one immune checkpoint inhibitor. In one embodiment, the method comprises at least the steps of: (a) obtaining a biological sample from a subject suffering from or suspected of suffering from HCC; (b) determining the concentration of LG2m in the biological sample; and (c) predicting that the subject is likely: (i) to respond to treatment with at least one immune checkpoint inhibitor if the LG2m concentration from the biological sample is lower than a reference level; or (ii) not to respond to treatment with at least one immune checkpoint inhibitor if the LG2m concentration form the biological sample is higher than a reference level. In yet another embodiment, also provided herein are methods of monitoring a subject suffering from HCC and receiving treatment with at least one immune checkpoint inhibitor. In one embodiment, the method comprises at least the steps of: (a) obtaining a biological sample from a subject suffering from HCC and receiving treatment with at least one immune checkpoint inhibitor; (b) determining the concentration of LG2m in the biological sample; and (c) continuing to treat the subject with at least one immune checkpoint inhibitor if the LG2m concentration determined in the biological sample is lower than a reference level or discontinuing treatment with the at least one immune checkpoint inhibitor or switching treatment to another immune checkpoint inhibitor or other treatment, if the LG2m concentration from the biological sample is higher than a reference level. As mentioned previously, the methods described herein comprise obtaining one or more biological samples from a subject (e.g., a mammal, such as a human) suffering from or suspected of having suffered from HCC. In some embodiments, the biological sample is from a subject suspected of suffering from HCC and not yet receiving treatment with an immune checkpoint inhibitor. In other embodiments, the biological sample is from a subject determined to be suffering from HCC and not yet receiving treatment with an immune checkpoint inhibitor. In still other embodiments, the biological sample is from a subject determined to be suffering from HCC and receiving treatment with at least one immune checkpoint inhibitor. In some embodiments, the biological sample is a serum sample. In other aspects, the biological sample is a plasma sample. In still other embodiments, the biological sample is a whole blood sample. Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 Any method or assay for measuring or determining the concentration (e.g., level or amount) of LG2m in a biological sample can be used in the methods described herein. In some embodiments, the concentration of LG2m can be measured or determined using an immunoassay, a clinical chemistry assay, a single molecule detection assay, cytometry, or any combinations thereof. In another embodiment, the concentration of LG2m can be measured or determined using an immunoassay. In yet another embodiment, the level or concentration of LG2m can be determined using the methods of U.S. Patent Publication No. 2014/0045196A1, the contents of which are herein incorporated by reference. For example, the method may include: (a) measuring the concentration of LG2m by: (i) contacting the biological sample with at least one first antibody (“at least one first capture antibody”) wherein the capture antibody specifically binds to an epitope on LG2m or a fragment of LG2m to form a capture antibody-LG2m complex; (ii) contacting the capture antibody-LG2m complex with at least one second antibody comprising at least one detectable label (“at least one first detection antibody”), wherein the detection antibody specifically binds to an epitope on LG2m that is not bound by the capture antibody and forms a capture antibody-LG2m-detection antibody complex; and (iii) determining the level of LG2m in the test sample based on the signal generated by the detectable label in the capture antibody-LG2m- detection antibody complex formed in (a)(ii). Any immunoassay may be utilized. The immunoassay may be an enzyme-linked immunoassay (ELISA), radioimmunoassay (RIA), a competitive inhibition assay, such as forward or reverse competitive inhibition assays, a fluorescence polarization assay, or a competitive binding assay, for example. The ELISA may be a sandwich ELISA. Specific immunological binding of the antibody to the marker can be detected via direct labels, such as fluorescent or luminescent tags, metals and radionuclides attached to the antibody or via indirect labels, such as alkaline phosphatase or horseradish peroxidase. The use of immobilized antibodies or fragments thereof may be incorporated into the immunoassay. The antibodies may be immobilized onto a variety of supports, such as magnetic or chromatographic matrix particles, the surface of an assay plate (such as microtiter wells), pieces of a solid substrate material, and the like. An assay strip can be prepared by coating the antibody or plurality of antibodies in an array on a solid support. This strip can then be dipped into the test Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 biological sample and then processed quickly through washes and detection steps to generate a measurable signal, such as a colored spot. Optionally, prior to contacting the biological sample with the at least one first capture antibody, the at least one first capture antibody can be bound to a solid support which facilitates the separation the capture antibody-LG2m-detection antibody complex from the biological sample. Any solid support known in the art can be used, including but not limited to, solid supports made out of polymeric materials in the forms of wells, tubes or beads. The antibody (or antibodies) can be bound to the solid support by adsorption, by covalent bonding using a chemical coupling agent or by other means known in the art, provided that such binding does not interfere with the ability of the antibody to bind the marker. Moreover, if necessary, the solid support can be derivatized to allow reactivity with various functional groups on the antibody. Such derivatization requires the use of certain coupling agents such as, but not limited to, maleic anhydride, N- hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. After the biological sample suspected of containing LG2m brought into contact with the at least one first capture antibody, the test sample is incubated in order to allow for the formation of a capture antibody (or multiple antibody)-LG2m-at least one detection antibody complex. The incubation can be carried out at a pH of from about 4.5 to about 10.0, at a temperature of from about 2° C to about 45° C, and for a period from at least about one (1) minute to about eighteen (18) hours, from about 2 to about 6 minutes, from about 3 to about 4 minutes, from about 10 to about 15 minutes, or about 18 to about 20 minutes. Once the concentration of LG2m is determined in a biological sample obtained from the subject, the concentration of LG2m is compared to a reference level. Specifically, a reference level of LG2m can be employed as a benchmark against which to assess results obtained upon assaying a biological sample for LG2m. Generally, in making such a comparison, the reference level of LG2m, is obtained by running or conducting a particular assay a sufficient number of times and under appropriate conditions such that a linkage or association of analyte presence, amount or concentration with a particular stage or endpoint of HCC. Typically, the reference level of LG2m is obtained with assays of reference subjects (or populations of subjects). In some embodiments, the reference level is about 10 pg/mL, about 15 pg/mL, about 20 pg/mL, about 25 pg/mL, about 30 pg/mL, about 35 pg/mL, about 40 pg/mL, about 45 pg/mL, about 50 pg/mL, about 55 pg/mL, about 60 pg/mL, about 65 pg/mL, about 70 pg/mL or about 75 pg/mL, about 80 pg/mL, Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 about 85 pg/mL, about 90 pg/mL, about 95 pg/mL or about 100 pg/mL. In some embodiments, the reference level is about 45 pg/mL. In still other embodiments, the reference level is about 50 pg/mL. In still yet other embodiments, the reference level is about 75 pg/mL. In still yet other embodiments, the reference level is about 100 pg/mL. In some embodiments, when the concentration of LG2m in the biological sample is lower than a reference level of LG2m, the method further comprises administering to the subject (e.g., such as a subject suffering from or suspected of having suffered from HCC but not yet receiving treatment with an immune checkpoint inhibitor) at least one immune checkpoint inhibitor. In some embodiments, when the concentration of LG2m in the biological sample is higher than a reference level of LG2m, no immune checkpoint inhibitor is administered to the subject (e.g., such as a subject suffering from or suspected of having suffered from HCC but not yet receiving treatment with an immune checkpoint inhibitor). In still other embodiments, in subjects suffering from or suspects of suffering from HCC, but not yet receiving treatment with at least one immune checkpoint inhibitor, when the concentration of LG2m in the biological sample is lower than a reference level of LG2m, a determination or prediction can be made that the subject is likely to respond to treatment with at least one immune checkpoint inhibitor. When such a determination or prediction is made, the method can further comprise administering at least one immune checkpoint inhibitor to a subject determined or predicted as likely to respond to said treatment. In some embodiments, in subjects suffering from or suspects of suffering from HCC, but not yet receiving treatment with at least one immune checkpoint inhibitor when the concentration of LG2m in the biological sample is higher than a reference level of LG2m, a determination or prediction can be made that the subject is not likely to respond to treatment with at least one immune checkpoint inhibitor. Such subjects are not treated with at least one immune checkpoint inhibitor but can be treated with other therapeutic agents. In yet other embodiments, when the concentration of LG2m in the biological sample is lower than a reference level of LG2m and the subject is suffering from HCC and receiving treatment with at least one immune checkpoint inhibitor, a decision can be made to continue to treat the subject with current (e.g., same) immune checkpoint inhibitor that the subject had been (previously) treated with. In other embodiments, when the concentration of LG2m in the biological sample is higher than a reference level of LG2m and the subject is suffering from HCC Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 and receiving treatment with at least one immune checkpoint inhibitor, treatment with the current immune checkpoint inhibitor can be discontinued. In some embodiments, treatments with the current immune checkpoint inhibitor can be discontinued indefinitely, or the subject can be administered an immune checkpoint inhibitor that is different than the immune checkpoint inhibitor that the subject was previously treated with and/or the subject can be administered a different therapeutic agent to treat the HCC. In some embodiments, at least one immune checkpoint inhibitor administered to the subject is atezolizumab, avelumab, cemiplimab, dostarlimab, ipilimumab, nivolumab, pembrolizumab, retifanlimab, toripalimab, tremelimumab, durvalumab or any combinations thereof. In some embodiments, the at least one immune checkpoint inhibitor is administered in combination with a second therapeutic agent. In some embodiments, the second therapeutic agent is at least one anti-angiogenesis drug. In some embodiments, the anti-angiogenesis drug is a vascular endothelial growth factor (VEGF) inhibitor, a tyrosine kinase inhibitor (TKI), a monoclonal antibody, an angiopoietin inhibitor, an mTOR inhibitor, an immune checkpoint and the like. In further embodiments, the at least one anti-angiogenesis drug is bevacizumab. In some embodiments, the method further comprises communicating the concentration of LG2m in a biological sample. In some embodiments, the method comprises communicating the concentration of a subject’s LG2m levels on or from at least one instrument. Suitable instruments are described herein, including point-of-care devices and non-point-of care devices that may contain a user interface that communicates by displaying the determination. As discussed, in some embodiments, the instrument contains software to execute one or more tasks. In some embodiments, the instrument contains software to automatically determine the next appropriate step in a method as described herein. For example, the instrument may contain software that determines the concentration of LG2m in a biological sample obtained from a subject. The software may display this determination, such as on a graphical user interface. In some embodiments, the instrument stores software that instructs a processor to execute a given task. In some embodiments, the software stores machine readable instructions that instruct a processor to execute a given task. The machine-readable instructions may be one or more executable programs or portion(s) of an executable program for execution by a computer. The programs may be embodied in software stored on a non-transitory computer readable storage medium such as a CD-ROM, a floppy disk, a hard drive, a DVD, a Blu-ray disk, or a memory Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 associated with the processors. Alternatively, the entire programs and/or parts thereof could alternatively be executed by a device other than the processors and/or embodied in firmware or dedicated hardware. Additionally or alternatively, processes may be implemented by one or more hardware circuits (e.g., discrete and/or integrated analog and/or digital circuitry, an FPGA, an ASIC, a comparator, an operational-amplifier (op-amp), a logic circuit, etc.) structured to perform the corresponding operation without executing software or firmware. The machine-readable instructions may be stored in one or more of a compressed format, an encrypted format, a fragmented format, a compiled format, an executable format, a packaged format, etc. Machine-readable instructions as described herein may be stored as data (e.g., portions of instructions, code, representations of code, etc.) that may be utilized to create, manufacture, and/or produce machine executable instructions. For example, the machine-readable instructions may be fragmented and stored on one or more storage devices and/or computing devices (e.g., servers). The machine-readable instructions may require one or more of installation, modification, adaptation, updating, combining, supplementing, configuring, decryption, decompression, unpacking, distribution, reassignment, compilation, etc. in order to make them directly readable, interpretable, and/or executable by a computing device and/or other machine. For example, the machine-readable instructions may be stored in multiple parts, which are individually compressed, encrypted, and stored on separate computing devices, wherein the parts when decrypted, decompressed, and combined form a set of executable instructions that implement a program such as that described herein. In another example, the machine-readable instructions may be stored in a state in which they may be read by a computer, but require addition of a library (e.g., a dynamic link library (DLL)), a software development kit (SDK), an application programming interface (API), etc. in order to execute the instructions on a particular computing device or other device. In another example, the machine-readable instructions may need to be configured (e.g., settings stored, data input, network addresses recorded, etc.) before the machine-readable instructions and/or the corresponding program(s) can be executed in whole or in part. Thus, the disclosed machine- readable instructions and/or corresponding program(s) are intended to encompass such machine- readable instructions and/or program(s) regardless of the particular format or state of the machine- readable instructions and/or program(s) when stored or otherwise at rest or in transit. Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 The machine-readable instructions described herein can be represented by any past, present, or future instruction language, scripting language, programming language, etc. For example, the machine-readable instructions may be represented using any of the following languages: C, C++, Java, C#, Perl, Python, JavaScript, HyperText Markup Language (HTML), Structured Query Language (SQL), Swift, etc. The machine-readable instructions may be stored on a non-transitory computer and/or machine readable medium such as a hard disk drive, a flash memory, a read-only memory, a compact disk, a digital versatile disk, a cache, a random-access memory and/or any other storage device or storage disk in which information is stored for any duration (e.g., for extended time periods, permanently, for brief instances, for temporarily buffering, and/or for caching of the information). As used herein, the term non-transitory computer readable medium is expressly defined to include any type of computer readable storage device and/or storage disk and to exclude propagating signals and to exclude transmission media. 3. Apparatus, Non-Transitory Machine-Readable Storage Medium, and Systems In some embodiments, disclosed herein are apparatus, machine-readable storage mediums and systems for use in implementing or performing the methods described in Section 2. More specifically, the apparatus, machine-readable storage mediums, and systems described herein can be used to determine the concentration (e.g., amount or level) of LG2m in one or more biological samples obtained from a subject, and communicate from an apparatus (e.g., such as a point-of-care, non-point-of-care, or a point-of-care and non-point-of-care apparatus), whether the concentration of LG2m is greater than or less than one or more reference or other levels. The term “apparatus” is used interchangeably with “device” or “instrument”. In another embodiment, the present disclosure relates to an apparatus, device, or instrument. The apparatus, device, or instrument contains software to execute one or more tasks, including the performance of the methods described in Section 2. In some embodiment, the apparatus, device, or instrument contains software to automatically determine the next appropriate step in the methods described herein. For example, the apparatus, device, or instrument may contain software that determines the amount or presence of an analyte of interest. The software may display this determination, such as on a graphical user interface. In some embodiments, the apparatus, device, or instruments stores software that instructs processor or processor circuitry to execute or instantiate a given task. In some Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 embodiments, the software stores machine-readable instructions that cause processor circuity to execute or instantiate a given task. The machine-readable instructions may be one or more executable programs or portion(s) of an executable program for execution by a computer. The programs may be embodied in software stored on a non-transitory computer readable storage medium such as a CD-ROM, a floppy disk, a hard drive, a DVD, a Blu-ray disk, or a memory associated with the processors. Alternatively, the entire programs and/or parts thereof could alternatively be executed by a device other than the processors and/or embodied in firmware or dedicated hardware. Additionally or alternatively, processes may be implemented by one or more hardware circuits (e.g., discrete and/or integrated analog and/or digital circuitry, an FPGA, an ASIC, a comparator, an operational-amplifier (op-amp), a logic circuit, etc.) structured to perform the corresponding operation without executing software or firmware. The machine-readable instructions may be stored in one or more of a compressed format, an encrypted format, a fragmented format, a compiled format, an executable format, a packaged format, etc. Machine readable instructions as described herein may be stored as data (e.g., portions of instructions, code, representations of code, etc.) that may be utilized to create, manufacture, and/or produce machine executable instructions. For example, the machine-readable instructions may be fragmented and stored on one or more storage devices and/or computing devices (e.g., servers). The machine-readable instructions may require one or more of installation, modification, adaptation, updating, combining, supplementing, configuring, decryption, decompression, unpacking, distribution, reassignment, compilation, etc. in order to make them directly readable, interpretable, and/or executable by a computing device and/or other machine. For example, the machine-readable instructions may be stored in multiple parts, which are individually compressed, encrypted, and stored on separate computing devices, wherein the parts when decrypted, decompressed, and combined form a set of executable instructions that implement a program such as that described herein. In another example, the machine-readable instructions may be stored in a state in which they may be read by a computer, but require addition of a library (e.g., a dynamic link library (DLL)), a software development kit (SDK), an application programming interface (API), etc. in order to execute the instructions on a particular computing device or other device. In another example, the machine-readable instructions may need to be configured (e.g., settings stored, data input, network addresses recorded, etc.) before the machine-readable instructions and/or the Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 corresponding program(s) can be executed in whole or in part. Thus, the disclosed machine- readable instructions and/or corresponding program(s) are intended to encompass such machine- readable instructions and/or program(s) regardless of the particular format or state of the machine- readable instructions and/or program(s) when stored or otherwise at rest or in transit. The machine-readable instructions described herein can be represented by any past, present, or future instruction language, scripting language, programming language, etc. For example, the machine-readable instructions may be represented using any of the following languages: C, C++, Java, C#, Perl, Python, JavaScript, HyperText Markup Language (HTML), Structured Query Language (SQL), Swift, etc. The machine-readable instructions may be stored on a non-transitory computer and/or non-transitory machine-readable medium such as a hard disk drive, a flash memory, a read-only memory, a compact disk, a digital versatile disk, a cache, a random-access memory and/or any other storage device or storage disk in which information is stored for any duration (e.g., for extended time periods, permanently, for brief instances, for temporarily buffering, and/or for caching of the information). As used herein, the term “non-transitory computer readable medium” is defined to include any type of computer readable storage device and/or storage disk and to exclude propagating signals and to exclude transmission media. In some further aspects, disclosed herein is a system for: (1) evaluating whether a subject that is suffering from or suspected of suffering from HCC should be administered at least one immune checkpoint inhibitor (e.g., a subject not yet receiving treatment with at least one immune checkpoint inhibitor); (2) predicting whether a subject suffering from or suspected of suffering from HCC (e.g., a subject not yet receiving treatment with at least one immune checkpoint inhibitor) is likely to respond to treatment with at least one immune checkpoint inhibitor; and/or (3) monitoring a subject suffering from HCC and receiving treatment with at least one immune checkpoint inhibitor. The system comprises: a. a data-obtaining module to obtain data on the concentration (e.g., level or amount) of LG2m from one or more assays performed on at least one or more samples obtained from a subject suspected of suffering or suffering from HCC (e.g., such as a subject not yet receiving treatment with at least one immune checkpoint inhibitor) or a subject suffering from HCC and receiving treatment with at least one immune checkpoint inhibitor; b. an evaluation module to analyze the data to obtain: Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 i) a first evaluation result of the subject’sLG2m concentration is less than a reference level; ii) a second evaluation result of the subject’sLG2m concentration is greater than a reference level; and c. a data-outputting module to output the evaluation result (e.g., the first evaluation results or the second evaluation result), wherein the first evaluation result is associated with determining whether the subject is likely to respond to treatment with at least one immune checkpoint inhibitor (for a subject not yet receiving treatment with at least one immune checkpoint inhibitor), should be administered at least one immune checkpoint inhibitor (for a subject not yet receiving treatment with at least one immune checkpoint inhibitor, or should continue treatment with at least one immune checkpoint inhibitor (for a subject previously diagnosed with HCC and receiving treatment with at least one immune checkpoint inhibitor); and the second evaluation result is associated with determining whether the subject is not likely to respond to treatment with at least one immune checkpoint inhibitor (for a subject not yet receiving treatment with at least one immune checkpoint inhibitor), should not be administered at least one immune checkpoint inhibitor (for subject’s not yet receiving treatment with at least one immune checkpoint inhibitor, or should discontinue treatment with at least one immune checkpoint inhibitor (for subject’s previously diagnosed with HCC and receiving treatment with at least one immune checkpoint inhibitor) and optionally be treated with a different immune checkpoint inhibitor and/or other therapeutic agent. In still other aspects of the above evaluation system, measuring the LG2m level is done by immunoassay. In still further aspects of the above evaluation system, measuring the LG2m level is done by the LG2m level is done by a clinical chemistry assay. In still further aspects of the above system, the assay is a point-of-care assay or single molecule detection. In still further aspects of the above system, the subject is a human subject. In further aspects, disclosed herein is a computer device that comprises a storage device having machine-readable instructions stored thereon, and a processor. The processor executes the machine-readable instructions to perform the steps of the above computer-implemented method, or the steps performed by the above evaluation system. Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 The instructions that are included in the system can be provided as written instructions, such as in a product insert, product manual, excel document, etc., on a mobile device (e.g., a smart phone), on a website, in an e-mail, or any combination thereof. 4. Kit Provided herein is a kit, which may be used to determine the concentration, of LG2m in a biological sample in a sample obtained from a subject. The kit can further comprise at least one capture antibody and at least one detection antibody. In yet further embodiments, kit can comprise instructions for assaying the test sample for at least one biomarker by immunoassay, e.g., chemiluminescent microparticle immunoassay, a clinical chemistry assay, or any other assay known in the art. Instructions included in kits can be affixed to packaging material or can be included as a package insert. While the instructions are typically written or printed materials they are not limited to such. Any medium capable of storing such instructions and communicating them to an end user is contemplated by this disclosure. Such media include, but are not limited to, electronic storage media (e.g., magnetic discs, tapes, cartridges, chips), optical media (e.g., CD ROM), and the like. As used herein, the term "instructions" can include the address of an internet site that provides the instructions. Alternatively or additionally, the kit can comprise a calibrator or control for the at least one biomarker and/or at least one container (e.g., tube, microtiter plates or strips, which can be already coated with the relevant biomarker for conducting the assay, and/or a buffer, such as an assay buffer or a wash buffer, either one of which can be provided as a concentrated solution, a substrate solution for the detectable label (e.g., an enzymatic label), or a stop solution. Preferably, the kit comprises all components, i.e., reagents, standards, buffers, diluents, etc., which are necessary to perform the assay. The instructions also can include instructions for generating a standard curve. In some embodiments, the kit is useful for assaying a test sample for LG2m and/or LG2m fragment. The kit comprises at least one component for assaying the test sample for LG2m (e.g. LG2m instructions for assaying the test sample. For example, the kit can comprise instructions for assaying the test sample for LG2m by immunoassay, e.g., chemiluminescent microparticle immunoassay. Instructions included in kits can be affixed to packaging material or can be included as a package insert. While the instructions are typically written or printed materials they are not limited to such. Any medium capable of storing such instructions and communicating them to an end user is contemplated by this disclosure. Such media include, but are not limited to, Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 electronic storage media (e.g., magnetic discs, tapes, cartridges, chips), optical media (e.g., CD ROM), and the like. The at least one component may include at least one composition comprising one or more isolated antibodies or antibody fragments thereof that specifically bind to LG2m. The antibody may be a LG2m capture antibody and/or a LG2m detection antibody. In some embodiments, the kit additionally comprises a nuclease. Alternatively or additionally, the kit can comprise a calibrator or control, e.g., purified, and optionally lyophilized, LG2m and/or at least one container (e.g., tube, microtiter plates or strips, which can be already coated with an anti-LG2m monoclonal antibody) for conducting the assay, and/or a buffer, such as an assay buffer or a wash buffer, either one of which can be provided as a concentrated solution, a substrate solution for the detectable label (e.g., an enzymatic label), or a stop solution. Preferably, the kit comprises all components, i.e., reagents, standards, buffers, diluents, etc., which are necessary to perform the assay. The instructions also can include instructions for generating a standard curve. The kit may further comprise reference standards for quantifying LG2m. The reference standards may be employed to establish standard curves for interpolation and/or extrapolation of LG2m concentrations. The reference standards may include a high LG2m concentration level, for example, about 10 pg/mL, about 15 pg/mL, about 20 pg/mL, about 25 pg/mL, about 30 pg/mL, about 35 pg/mL, about 40 pg/mL, about 45 pg/mL, about 50 pg/mL, about 55 pg/mL, about 60 pg/mL, about 65 pg/mL, about 70 pg/mL or about 75 pg/mL, about 80 pg/mL, about 85 pg/mL, about 90 pg/mL, about 95 pg/mL or about 100 pg/mL. Any antibodies, which are provided in the kit, such as recombinant antibodies specific for LG2m, can incorporate a detectable label, such as a fluorophore, radioactive moiety, enzyme, biotin/avidin label, chromophore, chemiluminescent label, or the like, or the kit can include reagents for labeling the antibodies or reagents for detecting the antibodies (e.g., detection antibodies) and/or for labeling the analytes (e.g., LG2m) or reagents for detecting the analyte (e.g., LG2m). The antibodies, calibrators, and/or controls can be provided in separate containers or pre- dispensed into an appropriate assay format, for example, into microtiter plates. Optionally, the kit includes quality control components (for example, sensitivity panels, calibrators, and positive controls). Preparation of quality control reagents is well-known in the art and is described on insert sheets for a variety of immunodiagnostic products. Sensitivity panel Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 members optionally are used to establish assay performance characteristics, and further optionally are useful indicators of the integrity of the immunoassay kit reagents, and the standardization of assays. The kit can also optionally include other reagents required to conduct a diagnostic assay or facilitate quality control evaluations, such as buffers, salts, enzymes, enzyme co-factors, substrates, detection reagents, and the like. Other components, such as buffers and solutions for the isolation and/or treatment of a test sample (e.g., pre-treatment reagents), also can be included in the kit. The kit can additionally include one or more other controls. One or more of the components of the kit can be lyophilized, in which case the kit can further comprise reagents suitable for the reconstitution of the lyophilized components. The various components of the kit optionally are provided in suitable containers as necessary, e.g., a microtiter plate. The kit can further include containers for holding or storing a sample (e.g., a container or cartridge for a urine, whole blood, plasma, or serum sample). Where appropriate, the kit optionally also can contain reaction vessels, mixing vessels, and other components that facilitate the preparation of reagents or the test sample. The kit can also include one or more instrument for assisting with obtaining a test sample, such as a syringe, pipette, forceps, measured spoon, or the like. If the detectable label is at least one acridinium compound, the kit can comprise at least one acridinium-9-carboxamide, at least one acridinium-9-carboxylate aryl ester, or any combination thereof. If the detectable label is at least one acridinium compound, the kit also can comprise a source of hydrogen peroxide, such as a buffer, solution, and/or at least one basic solution. If desired, the kit can contain a solid phase, such as a magnetic particle, bead, test tube, microtiter plate, cuvette, membrane, scaffolding molecule, film, filter paper, disc, or chip. If desired, the kit can further comprise one or more components, alone or in further combination with instructions, for assaying the test sample for another analyte, which can be a biomarker, such as a biomarker of traumatic brain injury or disorder. Finally, the kit can also contain one or more immune checkpoint inhibitors. EXAMPLES In hepatocellular carcinoma (HCC) patients with elevated serum LG2m levels, in the tumor peripheral area had an immunosuppressive tumor microenvironment. Additionally, these patients exhibit reduced levels of Th cells and CTL, crucial components for recognizing cancer Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 antigens. Sorafenib, a multiple receptor tyrosine kinase inhibitor, demonstrates comparable therapeutic efficacy in HCC patients with high serum LG2m levels compared to those with low LG2m levels. Conversely, the effectiveness of Atezolizumab and Bevacizumab (Atez + Bev), antibody drugs targeting PD-L1 and VEGFA, is diminished in HCC patients with high serum LG2m levels compared to those with low levels. In essence, serum LG2m measurement may serve as a determinant of the immune microenvironment in HCC and could potentially predict the therapeutic response to immune checkpoint inhibitors (ICI). The following examples are for the purposes of illustration only and are not intended to limit the scope of the claims. _{EXAMPLE 1} Firstly, the relationship between serum LG2m concentration and T-cell infiltration by immunohistochemistry was analyzed (Figure 1). It was found that when all types of T cells were stained, the infiltration of T cells was different between cancerous and non-cancerous areas. Additionally, it was found that T-cell infiltration into the tumor was low in resected liver cancer tissues with serum LG2m high (≥ 50 pg/ml). _{EXAMPLE 2} Single-cell spatial analysis was performed by CODEX (Figure 2). There was little infiltration of T cells into the tumor, and it was found that there were many CD90-positive cells at the tumor peripheral area in resected liver cancer tissues with serum LG2m high (≥50 pg/ml). _{EXAMPLE 3} From Cellular Neighborhoods Analysis, cellular diversity was high at the boundary between cancerous and non-cancer areas, and differences between CD4-positive and CD8-positive T cells (degree of Ki67 expression) were observed Figure 3). _{EXAMPLE 4} Results of single-cell spatial analysis by CODEX were shown in Figure 4. It was shown that CTL exists similarly in both resected HCC tissues with serum LG2m high and low. In resected HCC tissues with serum LG2m high (≥50 pg/ml), there is little infiltration of CTC that recognize cancer antigens (CD8+ Ki67+, CD8+ PD1+, CD8+ TIGIT3+, CD8+ PD1+ TIGIT3+) at the tumor peripheral area. Additionally, it was found that there are few CTL that recognize immune checkpoint-associated molecules in resected HCC tissues with serum LG2m high. Th cells existed similarly in both resected HCC tissues with LG2m high and low. In resected HCC tissues with Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 serum LG2m high, there is little infiltration of CTC that recognize cancer antigens (CD4+Ki67+, CD4+ PD1+, CD4+ TIGIT3+, CD4+ TIM3+, CD4+ PD1+ TIGIT3+, CD4+ PD1+ TIM3+) at the tumor peripheral area. Likewise, it was found that there are few Th cells that recognize immune checkpoint-associated molecules in resected HCC tissues with serum LG2m high. Immunosuppressive M2 macrophages (CD68+CD206-) infiltrate at the tumor peripheral area in resected HCC tissues with serum LG2m high, and CD144+vascular endothelial cells tend to be abundant. In HCC resected tissues with serum LG2m high, there are many CD90+CSCs and αSMA-positive fibroblasts at the tumor peripheral zone. _{EXAMPLE 5} To compare the therapeutic effect between sorafenib and combination of atezolizumab and bevacizumab (Atez + Bev), median PFS time and hazard ratio were calculated by Kaplan- Meier analysis (See Figure 5). The serum LG2m low group showed significantly longer median OS time when treated with Atez + Bev as in median PFS time. The results also indicate that the good therapeutic effect of Atez + Bev can be expected in the serum LG2m low group analysis (Figure 5). Median PFS time with all patients had significantly longer when treated with Atez + Bev. When divided into two groups by serum LG2m (cut off = 49.3 pg/mL), the serum LG2m low group had a significantly longer median PFS time when treated with Atez + Bev, although there was no difference in median PFS time in the serum LG2m high group when treated with Atez + Bev and sorafenib. The results indicated that the good therapeutic effect of Atez + Bev can be expected in the serum LG2m low group. _{EXAMPLE 6} The median OS time was calculated by Kaplan-Meier analysis (Figure 6). It will be readily apparent to those skilled in the art that other suitable modifications and adaptations of the methods of the present disclosure described herein are readily applicable and appreciable and may be made using suitable equivalents without departing from the scope of the present disclosure or the aspects and embodiments disclosed herein. Having now described the present disclosure in detail, the same will be more clearly understood by reference to the following examples, which are merely intended only to illustrate some aspects and embodiments of the disclosure and should not be viewed as limiting to the scope of the disclosure. The disclosures of all journal references, U.S. patents, and publications referred to herein are hereby incorporated by reference in their entireties. Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 The present disclosure has multiple aspects, illustrated by the non-limiting examples described herein. It is understood that the foregoing detailed description and accompanying examples are merely illustrative and are not to be taken as limitations upon the scope of the disclosure, which is defined solely by the appended claims and their equivalents. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Such changes and modifications, including without limitation those relating to the chemical structures, substituents, derivatives, intermediates, syntheses, compositions, formulations, or methods of use of the disclosure, may be made without departing from the spirit and scope thereof. For reasons of completeness, various aspects of the disclosure are set out in the following numbered clauses: Clause 1. A method of determining whether a subject suffering from or suspected of suffering from hepatocellular carcinoma (HCC) should be administered at least one immune checkpoint inhibitor, the method comprising the steps of: a. obtaining a biological sample from a subject suffering from or suspected of suffering from HCC; b. determining the concentration of laminin γ2 monomer (LG2m) in the biological sample; and c. administering at least one immune checkpoint inhibitor to the subject if the LG2m concentration from the biological sample is lower than a reference level or not administering at least one immune checkpoint inhibitor to the subject if the LG2m concentration from the biological sample is higher than a reference level. Clause 2. A method of predicting whether a subject suffering from or suspected of suffering from hepatocellular carcinoma (HCC) is likely to respond to treatment with at least one immune checkpoint inhibitor, the method comprising the steps of: a. obtaining a biological sample from a subject suffering from or suspected of suffering from HCC; b. determining the concentration of laminin γ2 monomer (LG2m) in the biological sample; and Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 c. predicting that the subject is likely: (i) to respond to treatment with at least one immune checkpoint inhibitor if the LG2m concentration from the biological sample is lower than a reference level; or (ii) not to respond to treatment with at least one immune checkpoint inhibitor if the LG2m concentration form the biological sample is higher than a reference level. Clause 3. The method of clause 2, further comprising administering at least one immune checkpoint inhibitor to the subject predicted as likely to respond to treatment with at least one immune checkpoint inhibitor. Clause 4. The method of any of clauses 1-3, wherein the biological sample is a plasma sample or a serum sample. Clause 5. The method of clause 4, wherein the biological sample is a serum sample. Clause 6. The method of any of clauses 1-5, wherein the concentration of LG2m in the biological sample is determined by an immunoassay, a clinical chemistry assay, a single molecule detection assay, cytometry, or any combinations thereof. Clause 7. The method of clause 6, wherein the concentration of LG2m in the biological sample is determined by an immunoassay. Clause 8. The method of any of clauses 1-7, wherein the reference level is about 10 pg/mL, about 15 pg/mL, about 20 pg/mL, about 25 pg/mL, about 30 pg/mL, about 35 pg/mL, about 40 pg/mL, about 45 pg/mL, about 50 pg/mL, about 55 pg/mL, about 60 pg/mL, about 65 pg/mL, about 70 pg/mL or about 75 pg/mL, about 80 pg/mL, about 85 pg/mL, about 90 pg/mL, about 95 pg/mL or about 100 pg/mL. Clause 9. The method of any of clauses 1-8 wherein the at least one immune checkpoint inhibitor is atezolizumab, avelumab, cemiplimab, dostarlimab, ipilimumab, nivolumab, pembrolizumab, retifanlimab, toripalimab, tremelimumab, durvalumab or any combinations thereof. Clause 10. The method of clause 9, wherein the at least one immune checkpoint inhibitor is administered in combination with a second therapeutic agent. Clause 11. The method of clause 10, wherein the second therapeutic agent is at least one anti-angiogenesis drug. Clause 12. The method of clause 11, wherein the at least one anti-angiogenesis drug is bevacizumab. Clause 13. The method of any of clauses 1-12, wherein the subject is a human. Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 Clause 14. A method of monitoring a subject suffering from hepatocellular carcinoma (HCC) and receiving treatment with at least one immune checkpoint inhibitor, the method comprising the steps of: a. obtaining a biological sample from a subject suffering from HCC and receiving treatment with at least one immune checkpoint inhibitor; b. determining the concentration of laminin γ2 monomer (LG2m) in the biological sample; and c. continuing to treat the subject with the at least one immune checkpoint inhibitor if the LG2m concentration from the biological sample is lower than a reference level or discontinuing treatment with the at least one immune checkpoint inhibitor if the LG2m concentration from the biological sample is higher than a reference level. Clause 15. The method of clause 14, wherein the biological sample is a plasma sample or a serum sample. Clause 16. The method of clause 15, wherein the biological sample is a serum sample. Clause 17. The method of any of clauses 14-16, wherein the concentration of LG2m in the biological sample is determined by an immunoassay, a clinical chemistry assay, a single molecule detection assay, cytometry, or any combinations thereof. Clause 18. The method of clause 17, wherein the concentration of LG2m in the biological sample is determined by an immunoassay. Clause 19. The method of any of clauses 14-18, wherein the reference level is about 10 pg/mL, about 15 pg/mL, about 20 pg/mL, about 25 pg/mL, about 30 pg/mL, about 35 pg/mL, about 40 pg/mL, about 45 pg/mL, about 50 pg/mL, about 55 pg/mL, about 60 pg/mL, about 65 pg/mL, about 70 pg/mL or about 75 pg/mL, about 80 pg/mL, about 85 pg/mL, about 90 pg/mL, about 95 pg/mL or about 100 pg/mL. Clause 20. The method of any of clauses 14-19 wherein the at least one immune checkpoint inhibitor is atezolizumab, avelumab, cemiplimab, dostarlimab, ipilimumab, nivolumab, pembrolizumab, retifanlimab, toripalimab, tremelimumab, durvalumab or any combinations thereof. Clause 21. The method of any of clauses 14-20, wherein the subject is a human.

Claims

Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101 What is claimed is: 1. A method of determining whether a subject suffering from or suspected of suffering from hepatocellular carcinoma (HCC) should be administered at least one immune checkpoint inhibitor, the method comprising the steps of: a. obtaining a biological sample from a subject suffering from or suspected of suffering from HCC; b. determining the concentration of laminin γ2 monomer (LG2m) in the biological sample; and c. administering at least one immune checkpoint inhibitor to the subject if the LG2m concentration from the biological sample is lower than a reference level or not administering at least one immune checkpoint inhibitor to the subject if the LG2m concentration from the biological sample is higher than a reference level.

2. A method of predicting whether a subject suffering from or suspected of suffering from hepatocellular carcinoma (HCC) is likely to respond to treatment with at least one immune checkpoint inhibitor, the method comprising the steps of: a. obtaining a biological sample from a subject suffering from or suspected of suffering from HCC; b. determining the concentration of laminin γ2 monomer (LG2m) in the biological sample; and c. predicting that the subject is likely: (i) to respond to treatment with at least one immune checkpoint inhibitor if the LG2m concentration from the biological sample is lower than a reference level; or (ii) not to respond to treatment with at least one immune checkpoint inhibitor if the LG2m concentration form the biological sample is higher than a reference level.

3. The method of claim 2, further comprising administering at least one immune checkpoint inhibitor to the subject predicted as likely to respond to treatment with at least one immune checkpoint inhibitor.

4. The method of any of claims 1-3, wherein the biological sample is a plasma sample or a serum sample.

5. The method of claim 4, wherein the biological sample is a serum sample. Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101

6. The method of any of claims 1-5, wherein the concentration of LG2m in the biological sample is determined by an immunoassay, a clinical chemistry assay, a single molecule detection assay, cytometry, or any combinations thereof.

7. The method of claim 6, wherein the concentration of LG2m in the biological sample is determined by an immunoassay.

8. The method of any of claims 1-7, wherein the reference level is about 10 pg/mL, about 15 pg/mL, about 20 pg/mL, about 25 pg/mL, about 30 pg/mL, about 35 pg/mL, about 40 pg/mL, about 45 pg/mL, about 50 pg/mL, about 55 pg/mL, about 60 pg/mL, about 65 pg/mL, about 70 pg/mL or about 75 pg/mL, about 80 pg/mL, about 85 pg/mL, about 90 pg/mL, about 95 pg/mL or about 100 pg/mL.

9. The method of any of claims 1-8 wherein the at least one immune checkpoint inhibitor is atezolizumab, avelumab, cemiplimab, dostarlimab, ipilimumab, nivolumab, pembrolizumab, retifanlimab, toripalimab, tremelimumab, durvalumab or any combinations thereof.

10. The method of claim 9, wherein the at least one immune checkpoint inhibitor is administered in combination with a second therapeutic agent.

11. The method of claim 10, wherein the second therapeutic agent is at least one anti-angiogenesis drug.

12. The method of claim 11, wherein the at least one anti-angiogenesis drug is bevacizumab.

13. The method of any of claims 1-12, wherein the subject is a human.

14. A method of monitoring a subject suffering from hepatocellular carcinoma (HCC) and receiving treatment with at least one immune checkpoint inhibitor, the method comprising the steps of: a. obtaining a biological sample from a subject suffering from HCC and receiving treatment with at least one immune checkpoint inhibitor; b. determining the concentration of laminin γ2 monomer (LG2m) in the biological sample; and c. continuing to treat the subject with the at least one immune checkpoint inhibitor if the LG2m concentration from the biological sample is lower than a reference level or discontinuing treatment with the at least one immune checkpoint inhibitor if the LG2m concentration from the biological sample is higher than a reference level.

15. The method of claim 14, wherein the biological sample is a plasma sample or a serum sample. Client Ref No.15739WOO1 Attny Docket No. ABBTL- 43007.101

16. The method of claim 15, wherein the biological sample is a serum sample.

17. The method of any of claims 14-16, wherein the concentration of LG2m in the biological sample is determined by an immunoassay, a clinical chemistry assay, a single molecule detection assay, cytometry, or any combinations thereof.

18. The method of claim 17, wherein the concentration of LG2m in the biological sample is determined by an immunoassay.

19. The method of any of claims 14-18, wherein the reference level is about 10 pg/mL, about 15 pg/mL, about 20 pg/mL, about 25 pg/mL, about 30 pg/mL, about 35 pg/mL, about 40 pg/mL, about 45 pg/mL, about 50 pg/mL, about 55 pg/mL, about 60 pg/mL, about 65 pg/mL, about 70 pg/mL or about 75 pg/mL, about 80 pg/mL, about 85 pg/mL, about 90 pg/mL, about 95 pg/mL or about 100 pg/mL.

20. The method of any of claims 14-19 wherein the at least one immune checkpoint inhibitor is atezolizumab, avelumab, cemiplimab, dostarlimab, ipilimumab, nivolumab, pembrolizumab, retifanlimab, toripalimab, tremelimumab, durvalumab or any combinations thereof.

21. The method of any of claims 14-20, wherein the subject is a human.