{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T01:48:51Z","timestamp":1792547331354,"version":"4.5.0"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:00:00Z","timestamp":1728864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Urothelial bladder cancer is frequent and exhibits diverse prognoses influenced by molecular subtypes, urothelial subtype histology, and immune microenvironments. HLA-G, known for immune regulation, displays significant membranous expression in tumor tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied the protein expression of Human Leucocyte Antigen G (HLA-G) in 241 Muscle-Invasive Bladder Cancer (MIBC) patients, elucidating its potential clinical and biological significance. Protein expression levels were evaluated and correlated with molecular subtypes, histological characteristics, immune microenvironment markers, and survival outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>High HLA-G expression associates with poor overall survival (OS) and diseasespecific survival (DSS), independent of clinicopathological parameters. HLA-G expression varies among molecular subtypes and Urothelial Subtype Histology, e.g., elevated expression levels in basal\/squamous MIBC and those with sarcomatoid differentiation. Notably, HLA-G is increased in MIBC with an immune evasive microenvironment (high PD-L1 tumor cell expression, NK cell depletion, granzyme B (GZMB)\/CD8 ratio reduction, MHC class I (MHCI) expression reduction) that are characterized by immunosuppressive features and poor prognosis. Furthermore, HLA-G correlates with elevated levels of other immune checkpoint proteins (TIGIT, LAG3, CTLA-4), indicating its role in immune evasion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our findings underscore HLA-G\u2019s role as a potential prognostic marker and interesting immunotherapeutic target in MIBC. Its impact on immune evasion mechanisms and broad expression, coupled with associations withpoor survival and distinct tumor phenotypes, positions HLA-G as a promising protein for further exploration in developing targeted immunotherapies for MIBC patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1478196","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T04:28:59Z","timestamp":1728880139000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["HLA-G expression associates with immune evasion muscle-invasive urothelial cancer and drives prognostic 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