CN116083599A - For evaluating CD8 + T cell function marker and application thereof - Google Patents
For evaluating CD8 + T cell function marker and application thereof Download PDFInfo
- Publication number
- CN116083599A CN116083599A CN202211559584.7A CN202211559584A CN116083599A CN 116083599 A CN116083599 A CN 116083599A CN 202211559584 A CN202211559584 A CN 202211559584A CN 116083599 A CN116083599 A CN 116083599A
- Authority
- CN
- China
- Prior art keywords
- cell function
- evaluating
- cells
- cell
- nfat2
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 210000001744 T-lymphocyte Anatomy 0.000 title claims abstract description 139
- 230000003915 cell function Effects 0.000 title claims abstract description 59
- 239000003550 marker Substances 0.000 title claims description 10
- 108010018525 NFATC Transcription Factors Proteins 0.000 claims abstract description 49
- 102000002673 NFATC Transcription Factors Human genes 0.000 claims abstract description 49
- 230000014509 gene expression Effects 0.000 claims abstract description 44
- 108091049679 miR-20a stem-loop Proteins 0.000 claims abstract description 41
- 238000000034 method Methods 0.000 claims abstract description 29
- 108010043471 Core Binding Factor Alpha 2 Subunit Proteins 0.000 claims abstract description 25
- 102000002664 Core Binding Factor Alpha 2 Subunit Human genes 0.000 claims abstract description 20
- 210000004700 fetal blood Anatomy 0.000 claims abstract description 12
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 claims description 102
- 238000001514 detection method Methods 0.000 claims description 24
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 claims description 21
- 239000003153 chemical reaction reagent Substances 0.000 claims description 17
- 238000003753 real-time PCR Methods 0.000 claims description 13
- 238000005206 flow analysis Methods 0.000 claims description 12
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims description 9
- 102100037850 Interferon gamma Human genes 0.000 claims description 9
- 108010074328 Interferon-gamma Proteins 0.000 claims description 9
- 108010002350 Interleukin-2 Proteins 0.000 claims description 9
- 102000000588 Interleukin-2 Human genes 0.000 claims description 9
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 9
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 9
- 238000011156 evaluation Methods 0.000 claims description 9
- 102100025137 Early activation antigen CD69 Human genes 0.000 claims description 8
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 238000012216 screening Methods 0.000 claims description 6
- 230000005764 inhibitory process Effects 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 238000002123 RNA extraction Methods 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 102100036301 C-C chemokine receptor type 7 Human genes 0.000 claims description 3
- 101000716065 Homo sapiens C-C chemokine receptor type 7 Proteins 0.000 claims description 3
- 238000009472 formulation Methods 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- -1 CD45RA Proteins 0.000 claims description 2
- 239000012528 membrane Substances 0.000 claims description 2
- 102000039446 nucleic acids Human genes 0.000 claims description 2
- 108020004707 nucleic acids Proteins 0.000 claims description 2
- 150000007523 nucleic acids Chemical class 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 238000010839 reverse transcription Methods 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 210000004027 cell Anatomy 0.000 abstract description 38
- 230000001973 epigenetic effect Effects 0.000 abstract description 6
- 238000005516 engineering process Methods 0.000 abstract description 3
- 239000000090 biomarker Substances 0.000 abstract description 2
- 230000004913 activation Effects 0.000 description 28
- 238000010586 diagram Methods 0.000 description 25
- 230000002401 inhibitory effect Effects 0.000 description 17
- 108091030817 miR-20a-1 stem-loop Proteins 0.000 description 17
- 108091086627 miR-20a-2 stem-loop Proteins 0.000 description 17
- 108091069790 miR-20a-3 stem-loop Proteins 0.000 description 17
- 238000000684 flow cytometry Methods 0.000 description 15
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 14
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 14
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 11
- 239000002644 phorbol ester Substances 0.000 description 10
- PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 9
- PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 9
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 8
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 8
- 101001068133 Homo sapiens Hepatitis A virus cellular receptor 2 Proteins 0.000 description 8
- 101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 description 8
- 102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 description 8
- 108091043222 miR-181b stem-loop Proteins 0.000 description 8
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 102000004127 Cytokines Human genes 0.000 description 6
- 108090000695 Cytokines Proteins 0.000 description 6
- 108020004999 messenger RNA Proteins 0.000 description 6
- 102000040945 Transcription factor Human genes 0.000 description 5
- 108091023040 Transcription factor Proteins 0.000 description 5
- 230000003213 activating effect Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 230000024245 cell differentiation Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 210000005259 peripheral blood Anatomy 0.000 description 3
- 239000011886 peripheral blood Substances 0.000 description 3
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 2
- 241000713666 Lentivirus Species 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 230000006044 T cell activation Effects 0.000 description 2
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical group C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000030648 nucleus localization Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 108020005345 3' Untranslated Regions Proteins 0.000 description 1
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 102100030751 Eomesodermin homolog Human genes 0.000 description 1
- 101001064167 Homo sapiens Eomesodermin homolog Proteins 0.000 description 1
- 102000037982 Immune checkpoint proteins Human genes 0.000 description 1
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 238000003766 bioinformatics method Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000007711 cytoplasmic localization Effects 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 108091008042 inhibitory receptors Proteins 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000003071 memory t lymphocyte Anatomy 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000003762 quantitative reverse transcription PCR Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012106 screening analysis Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229960001967 tacrolimus Drugs 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6888—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Optical investigation techniques, e.g. flow cytometry
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56966—Animal cells
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/52—Assays involving cytokines
- G01N2333/521—Chemokines
- G01N2333/523—Beta-chemokines, e.g. RANTES, I-309/TCA-3, MIP-1alpha, MIP-1beta/ACT-2/LD78/SCIF, MCP-1/MCAF, MCP-2, MCP-3, LDCF-1or LDCF-2
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/52—Assays involving cytokines
- G01N2333/525—Tumor necrosis factor [TNF]
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/52—Assays involving cytokines
- G01N2333/54—Interleukins [IL]
- G01N2333/55—IL-2
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/52—Assays involving cytokines
- G01N2333/555—Interferons [IFN]
- G01N2333/57—IFN-gamma
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70503—Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
- G01N2333/70517—CD8
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70589—CD45
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70596—Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Analytical Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Hematology (AREA)
- Wood Science & Technology (AREA)
- Microbiology (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Biotechnology (AREA)
- Urology & Nephrology (AREA)
- Cell Biology (AREA)
- Biomedical Technology (AREA)
- Virology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dispersion Chemistry (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
The present invention discloses a method for evaluating CD8 + Markers of T cell function and uses thereof. The biomarker comprises any one or a combination of at least two of NFAT2, miR-20a or RUNX1. The invention is found in the umbilical cord blood CD8 for the first time + NFAT2, miR-20a and RUNX1 expression in T cells was significantly increased with CD8 + T cell function related NFAT2, miR-20a and RUNX1 can be used as a diagnostic for evaluating CD8 + Molecular markers of T cell function, combined with CAR-T cell technology, can evaluate CD8 simply and efficiently from epigenetic point of view + T cell function.
Description
Technical Field
The invention belongs to the technical field of biology, and relates to a marker for evaluating functions of CD8+T cells and application thereof.
Background
T cell depletion refers to the loss of T cell function in patients with common chronic infections and cancer. As a result of prolonged exposure to persistent antigens and inflammation, T cells gradually lose effector function, memory T cell characteristics also begin to be absent, inhibitory Receptor (IRS) expression increases and persists, epigenetic and transcriptional patterns change, metabolic patterns change, but such depletion is reversible, at least in part, primarily by preventing inhibitory pathways such as PD-1. The prior art mainly focuses on phenotype evaluation on CD8+T cell functions, and has single evaluation angle and poor accuracy.
CN108531544A discloses a miR-181b target gene screening method, which comprises the steps of amplifying primer RUNX1 under a PCR condition to obtain a determined sequence of RUNX1 gene 3' UTR region as a PCR product; then constructing a double-luciferase report system, detecting luciferase activity, and primarily identifying a target gene of miR-181 b; detecting the influence of miR-181b on the RUNX1 gene on the mRNA level by adopting an RT-qPCR method; and detecting the influence of miR-181b on the RUNX1 gene at the protein level by adopting a Western-blot method. The binding site between the RUNX 1' UTR region and the miR-181b is defined, the targeting regulation and control relationship between the miR-181b and the target gene RUNX1 is verified by utilizing the modern molecular biotechnology, the miR-181b can inhibit the expression of the RUNX1 gene at mRNA and protein levels, and the RUNX1 is defined as the target gene of the miR-181 b.
CN113677994a discloses a method and agent for assessing T cell function and predicting response to therapy by detecting the nuclear localization sequence of EOMES and/or post-translational modification in DNA binding motifs in T cells, including detecting acetylation, methylation of EOMES-641K, EOMES-641K-Me, EOMES-373K-Me in T cells or detecting the ratio of nuclear to cytoplasmic localization or the ratio of cytoplasmic to nuclear localization in T cells, but this method has problems of complex operation, high cost, etc.
In conclusion, the development of novel and effective markers for evaluating T cell functions is helpful to expand the evaluation standards of T cell functions, and has important significance in the field of evaluation of T cell functions and cancer treatment.
Disclosure of Invention
In view of the deficiencies and practical needs of the prior art, the present invention provides a method for evaluating CD8 + The T cell function marker and the application thereof solve the problems of complex operation, high cost, single evaluation angle and the like of the traditional T cell function evaluation method, and realize simple and efficient evaluation of the T cell function from the epigenetic angle.
In order to achieve the aim of the invention, the invention adopts the following technical scheme:
in a first aspect, the present invention provides a method for evaluating CD8 + A marker of T cell function, the marker comprising any one or a combination of at least two of NFAT2, miR-20a, or RUNX1.
The invention first discovers CD8 + The content of NFAT2, miR-20a and RUNX1 in T cells is obviously improved to CD8 + T cell function related NFAT2, miR-20a and RUNX1 can be used as assessment of CD8 + Molecular markers of T cell function, combined with CAR-T cell technology, can evaluate CD8 simply and efficiently from epigenetic point of view + T cell function.
In a second aspect, the present invention provides a method for evaluating CD8 according to the first aspect + Marker of T cell function and detection reagent for preparing same for evaluating CD8 + Use of a T cell functional product.
Preferably, the detection reagent comprises any one or a combination of at least two of an RNA extraction reagent, an RNA reverse transcription reagent, a quantitative PCR detection reagent, or a flow cytometric antibody.
Preferably, the RNA extraction reagent comprises: any one or a combination of at least two of Trizol, chloroform, isopropanol, absolute ethanol, 75% ethanol or enzyme-free water.
Preferably, the flow cytometric antibody comprises: any one or a combination of at least two of CD8, CD69, CCR7, CD45RA, IL-2, IFN-gamma or TNF-alpha.
In a third aspect, the present invention provides a method for evaluating CD8 + A product for T cell function comprising detecting a CD8 assay according to the first aspect + Reagents and/or apparatus for markers of T cell function.
Preferably, the product comprises a preparation, a nucleic acid membrane strip, a chip or a kit.
In a fourth aspect, the present invention provides a method for evaluating CD8 according to the first aspect + Markers for T cell function in assessment of CD8 + Use in T cell function.
In a fifth aspect, the present invention provides an assessment of CD8 + Methods of T cell functionComprising the following steps:
detection of the test sample for assessment of CD8 according to the first aspect + Levels of markers of T cell function;
according to the first aspect for evaluating CD8 + Assessment of the level of markers of T cell function CD8 + T cell function.
Preferably, the assessment is of CD8 + The method of T cell function includes:
detection of CD8 by multicolor flow analysis + Expression of related indicators on T cells.
Preferably, the sample to be tested comprises CD8 of cord blood origin + T cells, adult peripheral blood derived CD8 + T cells.
Preferably, the method is useful for applications other than disease diagnosis purposes, the specific application content including: assessment of CD8 from cord blood or adult peripheral blood for scientific experiments + T cell function; auxiliary screening and evaluation of CD8 derived from peripheral blood of patients and the like + T cell function (non-clinical diagnostic use).
In a sixth aspect, the present invention provides a method for evaluating CD8 according to the first aspect + Markers of T cell function as targets for screening for inhibition or promotion of CD8 + Use of a formulation for the depletion of T cell function.
Preferably, the screening comprises evaluating CD8 based on the pre-and post-use comparison of the candidate formulation to the first aspect + Influence of markers of T cell function to determine whether candidate agents can be used to inhibit or promote CD8 + T cell function depletion.
Compared with the prior art, the invention has the following beneficial effects:
the invention detects the CD8 from the cord blood and evaluates the CD8 for the first time + Specific markers associated with T cell function as markers for assessment of CD8 + Biomarkers of T cell function to assess CD8 by detecting specific metabolite levels in plasma + T cell function, the simple and efficient assessment of T cell function from the epigenetic perspective is realized.
Drawings
FIG. 1 is a flow cytometric analysis of CD8 + A logic drawing of early activation and cell differentiation of T cells;
FIG. 2 is a flow cytometric analysis of CD8 + A gate logic diagram of the T cell cytokines IL-2, IFN-gamma and TNF-alpha;
FIG. 3A is a CD8 + T cell subpopulation ratio flow analysis plots;
FIG. 3B is a schematic diagram of CD8 after NFAT2 activation + A statistical result diagram of the proportional flow cell analysis of the naive T cells;
FIG. 4A is a schematic diagram of CD8 after NFAT2 activation + CD69 in T cells + Cell proportion flow analysis chart;
FIG. 4B is a schematic diagram of CD8 after NFAT2 activation + CD69 in T cells + Cell proportion flow cytometry analysis and statistics results;
FIG. 5A is a schematic diagram of CD8 after NFAT2 activation + IL-2 in T cells + Cell proportion flow analysis chart;
FIG. 5B is a schematic diagram of CD8 after NFAT2 activation + IL-2 in T cells + Cell proportion flow cytometry analysis statistical result diagram;
FIG. 6A is a schematic diagram of CD8 after NFAT2 activation + IFN-gamma in T cells + Cell proportion flow analysis chart;
FIG. 6B is a diagram of CD8 after NFAT2 activation + IFN-gamma in T cells + Cell proportion flow cytometry analysis and statistics results;
FIG. 7A is a schematic diagram of CD8 after NFAT2 activation + TNF-alpha in T cells + Cell proportion flow analysis chart;
FIG. 7B is a schematic diagram of CD8 after NFAT2 activation + TNF-alpha in T cells + Cell proportion flow cytometry analysis statistical result diagram;
FIG. 8A is a schematic diagram of CD8 after NFAT2 activation + A graph of NFAT2 mRNA q-PCR detection results in T cells;
FIG. 8B is a schematic diagram of CD8 after NFAT2 activation + miR-20a-5p q-PCR detection result diagram in T cells;
FIG. 9A is a CD8 inhibiting NFAT2 activation + CD8 after expression of miR-20a in T cells + T cell subpopulation ratio flow analysis plots;
FIG. 9B is a CD8 inhibiting NFAT2 activation + CD8 after expression of miR-20a in T cells + A statistical result diagram of the proportional flow cell analysis of the naive T cells;
FIG. 10A is a schematic diagram of CD8 inhibiting NFAT2 activation + CD8 after expression of miR-20a in T cells + CD69 in T cells + Cell subpopulation proportional flow analysis plots;
FIG. 10B is a CD8 inhibiting NFAT2 activation + CD8 after expression of miR-20a in T cells + CD69 in T cells + Cell proportion flow cytometry analysis statistical result diagram;
FIG. 11A is a schematic diagram of CD8 inhibiting NFAT2 activation + CD8 after expression of miR-20a in T cells + IL-2 in T cells + Cell proportion flow analysis chart;
FIG. 11B is a CD8 inhibiting NFAT2 activation + CD8 after expression of miR-20a in T cells + IL-2 in T cells + Cell proportion flow cytometry analysis statistical result diagram;
FIG. 12A is a CD8 inhibiting NFAT2 activation + CD8 after expression of miR-20a in T cells + IFN-gamma in T cells + Cell proportion flow analysis chart;
FIG. 12B is a CD8 inhibiting NFAT2 activation + CD8 after expression of miR-20a in T cells + IFN-gamma in T cells + Cell proportion flow cytometry analysis statistical result diagram;
FIG. 13A is a CD8 inhibiting NFAT2 activation + CD8 after expression of miR-20a in T cells + TNF-alpha in T cells + Cell proportion flow analysis chart;
FIG. 13B is a CD8 inhibiting NFAT2 activation + CD8 after expression of miR-20a in T cells + TNF-alpha in T cells + Cell proportion flow cytometry analysis statistical result diagram;
FIG. 14A is a CD8 of AML patients and healthy people + miR-20a-5p q-PCR detection result diagram in T cells;
FIG. 14B shows CD8 of AML patient + q-PCR detection result graphs of PD-1, tim3, TIGIT and CLTA-4 in T cells;
FIG. 14C cord blood-derived CD8 for inhibiting miR-20a + mRNA q-PCR detection result graphs of PD-1, tim3, TIGIT and CLTA-4 in T cells;
FIG. 15A is a graph showing the results of cross analysis of database data predicting potential target genes that might regulate the transcription factors of PD-1, tim3, TIGIT and CLTA-4 and miR-20a-5 p;
FIG. 15B is a schematic representation of 5 of the 18 transcription factors predicted from database data regulating PD-1, tim3, TIGIT and CLTA-4 simultaneously;
FIG. 15C shows miR-20a inhibition of cord blood-derived CD8 + A RUNX1 mRNA q-PCR detection result graph in T cells;
FIG. 15D is a CD8 of AML patients and healthy people + A RUNX1 mRNA q-PCR detection result graph in T cells;
FIG. 16A is a schematic diagram of RUNX1 lentiviral-inducible expression vector construction;
FIG. 16B is a statistical plot of GFP expression in Jurkat cells induced by treatment with Doxcycline and infected with lentivirus, using flow cytometry;
FIG. 16C is a statistical plot of the mean fluorescence intensity of PD-1 in a flow cytometric analysis GFP positive cell subpopulation.
Detailed Description
The technical means adopted by the invention and the effects thereof are further described below with reference to the examples and the attached drawings. It is to be understood that the specific embodiments described herein are merely illustrative of the invention and are not limiting thereof.
The specific techniques or conditions are not identified in the examples and are described in the literature in this field or are carried out in accordance with the product specifications. The reagents or apparatus used were conventional products commercially available through regular channels, with no manufacturer noted.
Example 1
In this example, mononuclear cells were obtained from fresh cord blood by lymphocyte separation and density gradient centrifugation by in vitro culture, and CD8 from MiltenyiBiotec, germany + After the enrichment of the T cell magnetic bead antibody kit, the streaming antibody CD8 is sequentially added,CCR7 is separated from CD45RA after light-shading dyeing by a flow cytometry sorter + CD45RA + A kind of electronic device
A cell subpopulation. Flow cytometry sorting obtained->
After T cell activation treatment for 48h with T cell TransAct reagent from Miltenyi Biotec, germany, 70% of the activator-containing medium was aspirated, and after further incubation with fresh CTS complete medium for 5 days, the control group (NC), the activated NFAT2 group (phorbol ester/ionomycin, PMA group), and the inhibited NFAT2 (Tacrolimus, FK506 group) were subjected to treatment time calculation from the addition of the drug treatment, and the cells treated for 1 day, 4 days and 7 days were collected for the flow cell detection of cell subpopulations and cytokine and quantitative PCR detection of miR-20a expression, respectively, and 1 XBFA pretreatment was added 6h before cell collection to inhibit cytokine secretion out of cells.
FIGS. 3A and 3B show that phorbol ester/ionomycin treatment activates NFAT2 resulting in a reduced proportion of naive cells, i.e., activation of NFAT2 promotes CD8 + 
T cell differentiation. FIGS. 4A and 4B show that phorbol ester/ionomycin treatment activates NFAT2 to promote CD69 expression, i.e., activation of NFAT2 promotes CD8 + />
T cell activation; simultaneous detection of phorbol ester/ionomycin treatment activates CD8 of NFAT2 + />
Cytokine IL-2 (FIGS. 5A and 5B), IFN-gamma (FIGS. 6A and 6B) and TNF-alpha (FIGS. 7A and 7B) expression in T cells were significantly elevated, i.e., activation of NFAT2 promoted CD8 + />
Cytokine expression by T cells. Phorbol ester/ion detection by q-PCRTreatment with mycin activates CD8 of NFAT2 + />
Expression of the NFAT2a subtype (FIG. 8A) and miR-20a-5p (FIG. 8B) in T cells is also elevated, i.e., activation of NFAT2 also promotes CD8 + />
Expression of miR-20a-5p in T cells.
Example 2
This example observes CD8 promoted for NFAT2 activation by modulating miR-20a-5p expression + Effect of T cell function. Cd8+ was obtained as in example 1
After T cells are subjected to T cell TransAct reagent activation treatment for 48 hours and the activator is removed for further culture for 5 days, miR-20a agomir (up-regulated miR-20a-5 p) and Antagomir (miR-20 a-5p inhibition) are transfected through an electric breakdown mode. After 24h of electric breakdown treatment, collecting cells for flow cell detection of cell subsets and cytokines and quantitative PCR detection of miR-20a expression, adding 1 XBFA for pretreatment 6h before collecting the cells, and inhibiting the secretion of the cytokines outside the cells.
FIGS. 9A and 9B show the results of activating CD8 of NFAT2 in phorbol ester/ionomycin treatment + 
After inhibiting miR-20a-5p expression in T cells, the proportion of naive cells is not reduced, namely, the cell differentiation is inhibited; FIGS. 10A and 10B show that CD8 activating NFAT2 in phorbol ester/ionomycin treatment + />
After inhibiting miR-20a-5p expression in the T cells, CD69 expression is reduced, namely cell activation is reduced; simultaneous detection of CD8 activating NFAT2 upon phorbol ester/ionomycin treatment + />
Cytokine IL-2 after inhibition of miR-20a-5p expression in T cells (FIGS. 11A and 11A11B) Both IFN-gamma (FIGS. 12A and 12B) and TNF-alpha (FIGS. 13A and 13B) expression were significantly reduced, i.e., cytokine expression was reduced.
Example 3
This example compares CD8 from Acute Myeloid Leukemia (AML) patients by transcriptome sequencing, bioinformatics analysis and quantitative PCR + T cells, verification of NFAT2/miR-20a-5p signal axis abnormality on cord blood CD8 + Effect of T cell function. The results of FIGS. 14A and 14B show that AML patients have CD8 + The expression level of miR-20a-5p in T cells is lower than that of healthy people, and the expression levels of PD-1, tim-3, TIGIT and CTLA-4 are obviously higher than those of healthy people. FIG. 14C shows that activating CD8 of NFAT2 in phorbol ester/ionomycin treatment + 
CD8 after inhibiting miR-20a-5p expression in T cells + The expression level of PD-1, tim3, TIGIT and CLTA-4 in T cells is obviously improved, and the expression level is compared with that of CD8 of AML patient + The trends in T cells are similar. By means of database data screening analysis, 18 of the transcription factors which are likely to regulate PD-1, tim3, TIGIT and CLTA-4 were found to be potential target genes of miR-20a-5p (FIG. 15A), and further analysis of these 18 transcription factors revealed that 5 transcription factors simultaneously regulated PD-1, tim3, TIGIT and CLTA-4 (FIG. 15B), with the greatest change in expression being RUNX1. The q-PCR assay showed that activated CD8 of NFAT2 upon phorbol ester/ionomycin treatment + />
CD8 after inhibiting miR-20a-5p expression in T cells + The expression level of RUNX1 in T cells was significantly increased (fig. 15C), and the trend was also similar to that of CD8 in AML patients + Trends in T cells were similar (fig. 15D). These results suggest that NFAT2/miR-20a-5p signal axis abnormalities cause CD8 to cord blood + The phenotype of reduced T cell presentation function resembles that of CD8 in AML patients + T cell depletion phenotype
Further by constructing a RUNX1 lentiviral expression vector (FIG. 16A) for Doxcycline (DOX) -induced expression, the lentivirus was packaged and then infected with Jurkat cells (human T cells were simulated to some extent)By adding Doxcycline at different concentrations to the culture medium, flow cytometry analysis detects GFP expression and PD-1 expression in GFP positive subpopulations, and the results of fig. 16B and 16C show that, after Doxcycline treatment induces RUNX1 expression, the proportion of PD-1 positive cells and the average PD-1 fluorescence intensity in the RUNX1 overexpression group (RUNX 1 UP) are significantly UP-regulated compared to the control group (RUNX 1 CK). This also further demonstrates that high RUNX1 expression may mediate cord blood CD8 through up-regulation of immune checkpoints such as PD-1 + T cells are in a depleted phenotype.
As described above, the present invention was found for the first time in cord blood CD8 + NFAT2, miR-20a and RUNX1 expression in T cells was significantly increased with CD8 + T cell function related NFAT2, miR-20a and RUNX1 can be used as a diagnostic for evaluating CD8 + Molecular markers of T cell function, combined with CAR-T cell technology, can evaluate CD8 simply and efficiently from epigenetic point of view + T cell function.
The applicant states that the detailed method of the present invention is illustrated by the above examples, but the present invention is not limited to the detailed method described above, i.e. it does not mean that the present invention must be practiced in dependence upon the detailed method described above. It should be apparent to those skilled in the art that any modification of the present invention, equivalent substitution of raw materials for the product of the present invention, addition of auxiliary components, selection of specific modes, etc., falls within the scope of the present invention and the scope of disclosure.
Claims (10)
1. For evaluating CD8 + A marker of T cell function, characterized in that the marker comprises any one or a combination of at least two of NFAT2, miR-20a or RUNX1.
2. The method for evaluating CD8 of claim 1 + Marker of T cell function and detection reagent for preparing same for evaluating CD8 + Use of a T cell functional product.
3. The use according to claim 2, wherein the detection reagent comprises any one or a combination of at least two of an RNA extraction reagent, an RNA reverse transcription reagent, a quantitative PCR detection reagent or a flow cytometric antibody;
preferably, the RNA extraction reagent comprises: any one or a combination of at least two of Trizol, chloroform, isopropanol, absolute ethanol, 75% ethanol or absolute water;
preferably, the flow cytometric antibody comprises: any one or a combination of at least two of CD8, CD69, CCR7, CD45RA, IL-2, IFN-gamma or TNF-alpha.
4. For evaluating CD8 + A product of T cell function, comprising detecting the product of claim 1 for evaluating CD8 + Reagents and/or apparatus for markers of T cell function.
5. The method for evaluating CD8 according to claim 4 + A product of T cell function, characterized in that the product comprises a preparation, a nucleic acid membrane strip, a chip or a kit.
6. The method for evaluating CD8 of claim 1 + Markers for T cell function in assessment of CD8 + Use in T cell function.
7. Assessment of CD8 + A method of T cell function, the method comprising:
detection of CD8 for evaluation according to claim 1 in a sample to be tested + Levels of markers of T cell function;
the method for evaluating CD8 according to claim 1 + Assessment of the level of markers of T cell function CD8 + T cell function.
8. The method of claim 7, wherein the evaluating CD8 + The method of T cell function includes:
detection of CD8 by multicolor flow analysis + Expression of related indicators on T cells.
9. The method of claim 7, wherein the sample to be tested is cord blood-derived CD8 + T cells.
10. The method for evaluating CD8 of claim 1 + Markers of T cell function as targets for screening for inhibition or promotion of CD8 + Use of a formulation with depleted T cell function;
preferably, the screening comprises the use of the candidate agent of claim 1 for assessment of CD8 based on both pre-and post-use + Influence of markers of T cell function to determine whether candidate agents can be used to inhibit or promote CD8 + T cell function depletion.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211559584.7A CN116083599A (en) | 2022-12-06 | 2022-12-06 | For evaluating CD8 + T cell function marker and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211559584.7A CN116083599A (en) | 2022-12-06 | 2022-12-06 | For evaluating CD8 + T cell function marker and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116083599A true CN116083599A (en) | 2023-05-09 |
Family
ID=86185890
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211559584.7A Pending CN116083599A (en) | 2022-12-06 | 2022-12-06 | For evaluating CD8 + T cell function marker and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116083599A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019084495A1 (en) * | 2017-10-27 | 2019-05-02 | The Trustees Of The University Of Pennsylvania | Identifying epigenetic and transcriptional targets to prevent and reverse t cell exhaustion |
| CN114072166A (en) * | 2019-05-14 | 2022-02-18 | 泰加生物工艺学公司 | Compositions and methods for treating T cell depletion |
-
2022
- 2022-12-06 CN CN202211559584.7A patent/CN116083599A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019084495A1 (en) * | 2017-10-27 | 2019-05-02 | The Trustees Of The University Of Pennsylvania | Identifying epigenetic and transcriptional targets to prevent and reverse t cell exhaustion |
| CN114072166A (en) * | 2019-05-14 | 2022-02-18 | 泰加生物工艺学公司 | Compositions and methods for treating T cell depletion |
Non-Patent Citations (6)
| Title |
|---|
| LAURA FONTANA等: "MicroRNAs 17-5p–20a–106a control monocytopoiesis through AML1 targeting and M-CSF receptor upregulation", NATURE CELL BIOLOGY, vol. 9, no. 7, pages 775, XP002473507, DOI: 10.1038/ncb1613 * |
| STEFANO ROSSETTI 等: "RUNX1: A MicroRNA Hub in Normal and Malignant Hematopoiesis", INT J MOL SCI., vol. 14, no. 1, pages 1566 - 1588, XP055100989, DOI: 10.3390/ijms14011566 * |
| SUO-YU ZHU等: "miR-20a inhibits the killing effect of natural killer cells to cervical cancer cells by downregulating RUNX1", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 505, no. 1, pages 309 - 361 * |
| YIKAI ZHANG等: "The role of NFAT2/miR-20a-5p signaling pathway in the regulation of CD8+ naïve T cells activation and differentiation", IMMUNOBIOLOGY, vol. 226, no. 4, pages 1 - 8 * |
| ZHOUTING TUO等: "RUNX1 is a promising prognostic biomarker and related to immune infiltrates of cancer-associated fibroblasts in human cancers", BMC CANCER, vol. 22, no. 523, pages 1 - 16 * |
| 乔治•C.普伦德加斯特等: "THOMAS造血干细胞移植", vol. 1, 北京：中国科学技术出版社, pages: 148 - 150 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Løvendorf et al. | MicroRNA-223 and miR-143 are important systemic biomarkers for disease activity in psoriasis | |
| Jikuzono et al. | The miR-221/222 cluster, miR-10b and miR-92a are highly upregulated in metastatic minimally invasive follicular thyroid carcinoma | |
| Shirahata et al. | Gene expression-based molecular diagnostic system for malignant gliomas is superior to histological diagnosis | |
| Xu-Monette et al. | Clinical features, tumor biology, and prognosis associated with MYC rearrangement and Myc overexpression in diffuse large B-cell lymphoma patients treated with rituximab-CHOP | |
| Yamamoto et al. | Decreased miR-192 expression in peripheral blood of asthmatic individuals undergoing an allergen inhalation challenge | |
| Kojima et al. | Biomarkers for precision medicine in bladder cancer | |
| Zhang et al. | Tumor-selective replication herpes simplex virus-based technology significantly improves clinical detection and prognostication of viable circulating tumor cells | |
| WO2010147961A1 (en) | Methods and markers for predicting responses to chemotherapy | |
| Hartana et al. | Long noncoding RNA MIR4435-2HG enhances metabolic function of myeloid dendritic cells from HIV-1 elite controllers | |
| Pogosova-Agadjanyan et al. | Identification of radiation-induced expression changes in nonimmortalized human T cells | |
| Qin et al. | MicroRNA-184 acts as a potential diagnostic and prognostic marker in epithelial ovarian cancer and regulates cell proliferation, apoptosis and inflammation | |
| Xu et al. | Downregulated cytotoxic CD8+ T-cell identifies with the NKG2A-soluble HLA-E axis as a predictive biomarker and potential therapeutic target in keloids | |
| Zheng et al. | MiRNA-155 and miRNA-132 as potential diagnostic biomarkers for pulmonary tuberculosis: A preliminary study | |
| Xu et al. | MiR-650 inhibits the progression of glioma by targeting FAM83F. | |
| CN110643697A (en) | Application of peripheral blood mononuclear cell hsa-miR-874-3p as active tuberculosis marker | |
| KR20220163971A (en) | Thyroid cancer prognosis and treatment methods | |
| Rao et al. | Identification of plasma exosomes long non-coding RNA HAGLR and circulating tumor cells as potential prognosis biomarkers in non-small cell lung cancer | |
| WO2019005762A1 (en) | Treatment of non-small cell lung cancer | |
| Alsadhan et al. | CD49d expression identifies a biologically distinct subtype of chronic lymphocytic leukemia with inferior progression-free survival on BTK inhibitor therapy | |
| CN116083599A (en) | For evaluating CD8 + T cell function marker and application thereof | |
| US20160298198A1 (en) | Method for predicting development of melanoma brain metastasis | |
| US20230014092A1 (en) | Materials and methods for monitoring inflammation | |
| WO2019018764A1 (en) | Methods for determining response to parp inhibitors | |
| Chauhan et al. | Transcriptional and secretomic profiling of epidermal cells exposed to alpha particle radiation | |
| Wu et al. | Probe signal values in mRNA arrays imply an excessive involvement of neutrophil FCGR1 in tuberculosis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |