UBE 2 C ‐Mediated CD 147‐ CTLA ‐4 Axis Promotes T Cell Exhaustion and Immunosuppressive Microenvironment in Bladder Cancer
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2026
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| _version_ | 1867016092856090624 |
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| author | Xuwei Hong Ting Hong Xinyu Liu Peixiu Yao Weiqiang Lin Guoyuan Liu Huihong Guan Yonghai Zhang |
| author_facet | Xuwei Hong Ting Hong Xinyu Liu Peixiu Yao Weiqiang Lin Guoyuan Liu Huihong Guan Yonghai Zhang Xuwei Hong Ting Hong Xinyu Liu Peixiu Yao Weiqiang Lin Guoyuan Liu Huihong Guan Yonghai Zhang |
| collection | Wiley Open Access |
| contents | UBE 2 C ‐Mediated CD 147‐ CTLA ‐4 Axis Promotes T Cell Exhaustion and Immunosuppressive Microenvironment in Bladder Cancer Xuwei Hong Ting Hong Xinyu Liu Peixiu Yao Weiqiang Lin Guoyuan Liu Huihong Guan Yonghai Zhang Cancer Science 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. 10.1111/cas.70430 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| doi_str_mv | 10.1111/cas.70430 |
| format | Artículo Open Access |
| id | wiley_oa_10_1111_cas_70430 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| publishDate | 2026 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | UBE 2 C ‐Mediated CD 147‐ CTLA ‐4 Axis Promotes T Cell Exhaustion and Immunosuppressive Microenvironment in Bladder Cancer Xuwei Hong Ting Hong Xinyu Liu Peixiu Yao Weiqiang Lin Guoyuan Liu Huihong Guan Yonghai Zhang Cancer Science UBE 2 C ‐Mediated CD 147‐ CTLA ‐4 Axis Promotes T Cell Exhaustion and Immunosuppressive Microenvironment in Bladder Cancer Xuwei Hong Ting Hong Xinyu Liu Peixiu Yao Weiqiang Lin Guoyuan Liu Huihong Guan Yonghai Zhang Cancer Science 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. 10.1111/cas.70430 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| title | UBE 2 C ‐Mediated CD 147‐ CTLA ‐4 Axis Promotes T Cell Exhaustion and Immunosuppressive Microenvironment in Bladder Cancer |
| topic | Cancer Science |
| url | https://onlinelibrary.wiley.com/doi/10.1111/cas.70430 |