Biomarker: TIM-3

Histology type: endometrial serous carcinomas

Country: USA

Region: TX

Followed up time :

Subgroup 1 name : positive

Subgroup 1 number: 10

Subgroup 2 name: negative

Subgroup 2 number: 88

Conclusion: In conclusion, PD-L1, TIM-3 and B7-H3 may be potential therapeutic targets in selected patients with ESC. Further investigation of their roles as predictive biomarkers is needed.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : expression

Expression elevation: For all three immune checkpoint markers, cutoff scores of ≥1% for TPS and ≥1 for CPS were used to define positivity, and additional cutoffs (10, 20, and 50) were used to further analyze the significance of immune checkpoint expression. Due to the lack of established criteria for assessment of TIM-3 and B7-H3, the same scoring systems and positivity thresholds used for PD-L1 assessment were applied.

Statictics: Median;Range

Cohort age: 64 (49–83)

Funtion Uniprot: Cell surface receptor implicated in modulating innate and adaptive immune responses. Generally accepted to have an inhibiting function. Reports on stimulating functions suggest that the activity may be influenced by the cellular context and/or the respective ligand (PubMed:24825777). Regulates macrophage activation (PubMed:11823861). Inhibits T-helper type 1 lymphocyte (Th1)-mediated auto- and alloimmune responses and promotes immunological tolerance (PubMed:14556005). In CD8+ cells attenuates TCR-induced signaling, specifically by blocking NF-kappaB and NFAT promoter activities resulting in the loss of IL-2 secretion. The function may implicate its association with LCK proposed to impair phosphorylation of TCR subunits, and/or LGALS9-dependent recruitment of PTPRC to the immunological synapse (PubMed:24337741, PubMed:26492563). In contrast, shown to activate TCR-induced signaling in T-cells probably implicating ZAP70, LCP2, LCK and FYN (By similarity). Expressed on Treg cells can inhibit Th17 cell responses (PubMed:24838857). Receptor for LGALS9 (PubMed:16286920, PubMed:24337741). Binding to LGALS9 is believed to result in suppression of T-cell responses; the resulting apoptosis of antigen-specific cells may implicate HAVCR2 phosphorylation and disruption of its association with BAG6. Binding to LGALS9 is proposed to be involved in innate immune response to intracellular pathogens. Expressed on Th1 cells interacts with LGALS9 expressed on Mycobacterium tuberculosis-infected macrophages to stimulate antibactericidal activity including IL-1 beta secretion and to restrict intracellular bacterial growth (By similarity). However, the function as receptor for LGALS9 has been challenged (PubMed:23555261). Also reported to enhance CD8+ T-cell responses to an acute infection such as by Listeria monocytogenes (By similarity). Receptor for phosphatidylserine (PtSer); PtSer-binding is calcium-dependent. May recognize PtSer on apoptotic cells leading to their phagocytosis. Mediates the engulfment of apoptotic cells by dendritic cells. Expressed on T-cells, promotes conjugation but not engulfment of apoptotic cells. Expressed on dendritic cells (DCs) positively regulates innate immune response and in synergy with Toll-like receptors promotes secretion of TNF-alpha. In tumor-imfiltrating DCs suppresses nucleic acid-mediated innate immune repsonse by interaction with HMGB1 and interfering with nucleic acid-sensing and trafficking of nucleid acids to endosomes (By similarity). Expressed on natural killer (NK) cells acts as a coreceptor to enhance IFN-gamma production in response to LGALS9 (PubMed:22323453). In contrast, shown to suppress NK cell-mediated cytotoxicity (PubMed:22383801). Negatively regulates NK cell function in LPS-induced endotoxic shock (By similarity).

UniProt ID: Q8TDQ0

UniProt Link: https://www.uniprot.org/uniprotkb/Q8TDQ0/entry

Biological function from UniProt: #Adaptive immunity #Immunity #Inflammatory response #Innate immunity

Molecular function from UniProt:

Tissue specificity from UniProt: Expressed in T-helper type 1 (Th1) lymphocytes. Expressed on regulatory T (Treg) cells after TCR stimulation. Expressed in dendritic cells and natural killer (NK) cells. Expressed in epithelial tissues. Expression is increased on CD4+ and CD8+ T-cells in chronic hepatitis C virus (HCV) infection. In progressive HIV-1 infection, expression is up-regulated on HIV-1-specific CD8 T-cells.

Subcellular UniProt: #Cell junction #Cell membrane #Membrane

Alternative name from UniProt:

Caution: Experimental results based on the injection of HAVCR2/TIM-3 antibodies or use of HAVCR2/TIM-3-Fc fusion proteins can reflect changes in the activity of several cell types and pathways as HAVCR2/TIM-3 is expressed by multiple immune cell types.

Recommended name: Hepatitis A virus cellular receptor 2

Gene name from HGNC: HAVCR2 (CD366, FLJ14428, Tim-3, TIM3, TIMD3)

CD antigen name: CD366

HPA class: CD markers Disease related genes

AlphaFold DB: Q8TDQ0

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q8TDQ0

HPA link: https://www.proteinatlas.org/ENSG00000135077-HAVCR2

Tissue specificity RNA from HPA: Tissue enhanced (lymphoid tissue)

Tissue expression from HPA: Cytoplasmic expression in a subset of lymphoid cells.

Single cell type specificity Cell type enhanced (Hofbauer cells, NK-cells, Schwann cells, Macrophages, Langerhans cells, Proximal tubular cells, monocytes)

Immune cell specificity: Group enriched (myeloid DC, NK-cell, intermediate monocyte, classical monocyte, non-classical monocyte)

Subcellular summary HPA Not available

Cancer prognostic summary HPA Gene product is not prognostic

Pathology link: https://www.proteinatlas.org/ENSG00000135077-HAVCR2/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000135077-HAVCR2/pathology/endometrial+cancer

Survival figure legend: Kaplan–Meier curves of progression-free survival (PFS) and overall survival (OS) and correlation with TIM-3 and B7-H3 expression.

Survival curve link: https://ars.els-cdn.com/content/image/1-s2.0-S0893395222055077-gr6.jpg

Phenotype ID: No disease ID| 618398

Disease: No disease ID|T-cell lymphoma, subcutaneous panniculitis-like (SPTCL)

Note1: May be involved in T-cell exhaustion associated with chronic viral infections such as with human immunodeficiency virus (HIV) and hepatitic C virus (HCV)|Disease susceptibility is associated with variants affecting the gene represented in this entry

OMIM: 606652

OMIM link1: https://www.omim.org/entry/618398

OMIM link2: https://www.omim.org/entry/606652

HGNC ID: HGNC:18437

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:18437