MHC I级
细胞毒性T细胞
抗原处理
生物
主要组织相容性复合体
与抗原处理相关的转运体
河马信号通路
CD8型
癌症免疫疗法
细胞生物学
免疫疗法
抗原呈递
交叉展示
CTL公司*
效应器
抗原
癌症研究
免疫学
免疫系统
T细胞
生物化学
体外
作者
Peng Li,Liang Zhang,Huan Li,Xin Zhang,Li Su,Kai Wang,Ming‐Lin Yang,Xiaoyu Ma,Deshuai Zhang,Siliang Xiang,Yajun Duan,Tianzhi Wang,Chong Sun,Feng Wang,Desheng Lu,Minxian Qian,Zhongyuan Wang
出处
期刊:Cell Reports
[Elsevier]
日期:2024-04-01
卷期号:43 (4): 114003-114003
标识
DOI:10.1016/j.celrep.2024.114003
摘要
Summary
The major histocompatibility complex class I (MHC class I)-mediated tumor antigen processing and presentation (APP) pathway is essential for the recruitment and activation of cytotoxic CD8+ T lymphocytes (CD8+ CTLs). However, this pathway is frequently dysregulated in many cancers, thus leading to a failure of immunotherapy. Here, we report that activation of the tumor-intrinsic Hippo pathway positively correlates with the expression of MHC class I APP genes and the abundance of CD8+ CTLs in mouse tumors and patients. Blocking the Hippo pathway effector Yes-associated protein/transcriptional enhanced associate domain (YAP/TEAD) potently improves antitumor immunity. Mechanistically, the YAP/TEAD complex cooperates with the nucleosome remodeling and deacetylase complex to repress NLRC5 transcription. The upregulation of NLRC5 by YAP/TEAD depletion or pharmacological inhibition increases the expression of MHC class I APP genes and enhances CD8+ CTL-mediated killing of cancer cells. Collectively, our results suggest a crucial tumor-promoting function of YAP depending on NLRC5 to impair the MHC class I APP pathway and provide a rationale for inhibiting YAP activity in immunotherapy for cancer.
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