{"title":"UBE2C-Mediated CD147-CTLA-4 Axis Promotes T Cell Exhaustion and Immunosuppressive Microenvironment in Bladder Cancer","authors":"Xuwei Hong, Ting Hong, Xinyu Liu, Peixiu Yao, Weiqiang Lin, Guoyuan Liu, Huihong Guan, Yonghai Zhang","doi":"10.1111/cas.70430","DOIUrl":null,"url":null,"abstract":"<p>Despite immune checkpoint inhibitors (ICIs) having benefited bladder cancer (BCa) patients, their limited response rates urge elucidation of intrinsic resistance mechanisms. In this study, we demonstrated that ubiquitin conjugating enzyme E2C (UBE2C) promotes the proliferation, invasion, and migration of BCa and inhibits DNA damage, accompanied by a decrease in T cell abundance. In syngeneic C57BL/6 BCa models and BCa–CD8<sup>+</sup> T-cell cocultures, UBE2C silencing reduced CD147 and CTLA-4 abundance, restored IFN-γ, TNF-α, and TGF-β secretion, expanded CD3<sup>+</sup>CD8<sup>+</sup> subsets, and attenuated tumor growth, invasion, and migration. Conversely, UBE2C or CD147/CTLA-4 overexpression reinstated T-cell exhaustion and malignant progression. Targeting the UBE2C–CD147–CTLA-4 axis resensitizes BCa to immune attack, offering a rational strategy to extend the efficacy of current immunotherapies.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"117 9","pages":"2366-2378"},"PeriodicalIF":4.9000,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394930/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Science","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cas.70430","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/5/27 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Despite immune checkpoint inhibitors (ICIs) having benefited bladder cancer (BCa) patients, their limited response rates urge elucidation of intrinsic resistance mechanisms. In this study, we demonstrated that ubiquitin conjugating enzyme E2C (UBE2C) promotes the proliferation, invasion, and migration of BCa and inhibits DNA damage, accompanied by a decrease in T cell abundance. In syngeneic C57BL/6 BCa models and BCa–CD8+ T-cell cocultures, UBE2C silencing reduced CD147 and CTLA-4 abundance, restored IFN-γ, TNF-α, and TGF-β secretion, expanded CD3+CD8+ subsets, and attenuated tumor growth, invasion, and migration. Conversely, UBE2C or CD147/CTLA-4 overexpression reinstated T-cell exhaustion and malignant progression. Targeting the UBE2C–CD147–CTLA-4 axis resensitizes BCa to immune attack, offering a rational strategy to extend the efficacy of current immunotherapies.
期刊介绍：
Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports.
Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
