Biomarker: MHC class I status

Histology type: endometrial carcinoma

Country: USA

Region: Virginia

Followed up time :

Subgroup 1 name : loss of MHC class I expression

Subgroup 1 number: 44

Subgroup 2 name: MHC class I expression

Subgroup 2 number: 33

Conclusion: Tumoral MHC class I status may be an important factor to consider when selecting endometrial cancer patients for checkpoint inhibition.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : loss expression

Expression elevation: Tumoral staining was classified as “intact” (>90% of cells showing membranous and/or cytoplasmic expression of MHC class I), “subclonal loss” (10–90% MHC class I expression, with areas of retained MHC class I immediately juxtaposed with areas of negative tumor staining), or “diffuse loss” (<10% tumor cell expression of MHC class I). Occasional cases demonstrated retained MHC class I staining throughout the tumor but with varying intensity depending on the region; strongly staining regions were juxtaposed with mild to moderate staining regions. These tumors were classified as MHC class I intact due to the presence of appreciable membranous expression on all tumor cells.

Funtion Uniprot: Antigen-presenting molecule specialized in displaying microbial pyrimidine-based metabolites to alpha-beta T cell receptors (TCR) on innate-type mucosal-associated invariant T (MAIT) cells (PubMed:23051753, PubMed:26795251, PubMed:12794138, PubMed:19416870, PubMed:22692454, PubMed:23846752). In complex with B2M preferentially presents riboflavin-derived metabolites to semi-invariant TRAV1-2 TCRs on MAIT cells, guiding immune surveillance of the microbial metabolome at mucosal epithelial barriers (PubMed:26795251, PubMed:24695216, PubMed:20581831). Signature pyrimidine-based microbial antigens are generated via non-enzymatic condensation of metabolite intermediates of the riboflavin pathway with by-products arising from other metabolic pathways such as glycolysis. Typical potent antigenic metabolites are 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU) and 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), products of condensation of 5-amino-6-D-ribityaminouracil (5-A-RU) with glyoxal or methylglyoxal by-products, respectively (PubMed:24695216). May present microbial antigens to various TRAV1-2-negative MAIT cell subsets, providing for unique recognition of diverse microbes, including pathogens that do not synthesize riboflavin (PubMed:27527800, PubMed:31113973). Upon antigen recognition, elicits rapid innate-type MAIT cell activation to eliminate pathogenic microbes by directly killing infected cells (PubMed:24695216, PubMed:27527800, PubMed:23846752). During T cell development, drives thymic selection and post-thymic terminal differentiation of MAIT cells in a process dependent on commensal microflora (By similarity). Acts as an immune sensor of cancer cell metabolome (PubMed:31959982). May present a tumor-specific or -associated metabolite essential for cancer cell survival to a pan-cancer TCR consisting of TRAV38.2-DV8*TRAJ31 alpha chain paired with a TRBV25.1*TRBJ2.3 beta chain on a non-MAIT CD8-positive T cell clone (MC.7.G5), triggering T cell-mediated killing of a wide range of cancer cell types (PubMed:31959982).

UniProt ID: Q95460

UniProt Link: https://www.uniprot.org/uniprotkb/Q95460/entry

Biological function from UniProt: #Immunity #Innate immunity

Molecular function from UniProt:

Tissue specificity from UniProt: Ubiquitous (PubMed:7624800, PubMed:9780177). Low expression is detected in peripheral blood B cells, T cells, monocytes and in bronchial epithelial cells (at protein level) (PubMed:27043408). Expressed in plasmablasts or plasma B cells in the lamina propria of ileum, appendix and colon (at protein level) (PubMed:19760593). Highly expressed on a subset of CD45-positive CD3-positive thymocytes (at protein level) (PubMed:22692454).

Subcellular UniProt: #Cell membrane #Endoplasmic reticulum #Endosome #Golgi apparatus #Membrane

Alternative name from UniProt:

Caution: Reported to be associated with components of the peptide-loading complex, TAPBP, CALR, CANX and PDIA3 (PubMed:23457030, PubMed:12794138). This association in primary cells and its functional relevance is disputable, given that antigen presentation and MAIT cell activation is shown to be TAP1-TAP2 and proteasome-independent

Activity regulation: Usually inhibited by pterin-based metabolites such as 6-formylpterin (6-FP, a product of folic acid photodegradation). 6-FP competitively inhibits MAIT cell activation by 5-OP-RU (PubMed:28166217). Modulated by commonly prescribed anti-inflammatory drug metabolites. Inhibited by salicilates such as 3-formylsalicylic and 5-formylsalicylic acids. Activated by diclofenac and/or its hydroxy metabolites (PubMed:28166217)

Recommended name: Major histocompatibility complex class I-related gene protein

Gene name from HGNC: MR1 (HLALS)

HPA class: FDA approved drug targets

AlphaFold DB: Q95460

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q95460

HPA link: https://www.proteinatlas.org/ENSG00000153029-MR1

Tissue specificity RNA from HPA: Low tissue specificity

Single cell type specificity Low cell type specificity

Immune cell specificity: Low immune cell specificity

Subcellular summary HPA Located in Plasma membrane

Cancer prognostic summary HPA Gene product is not prognostic

Pathology link: https://www.proteinatlas.org/ENSG00000153029-MR1/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000153029-MR1/pathology/endometrial+cancer

OMIM: 600764

OMIM link2: https://www.omim.org/entry/600764

HGNC ID: HGNC:4975

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4975