CBX2 suppresses interferon signaling to diminish tumor immunogenicity via a noncanonical corepressor complex

• 成果类型: Article
• 署名作者: Lin, Yanxun; Jin, Huan; She, Yong; Zhang, Yiqun; Cui, Lei; Xie, Chunyuan; Liu, Yongxiang; Zhang, Huanling; Guo, Hui; Wu, Jiaxin; Li, Lin; Guo, Zixuan; Wang, Xiaojuan; Jiang, Wu; Chen, Xu; He, Shuai; Zhou, Penghui; Tan, Jing; Bei, Jin- Xin; Liu, Jinyun; Chen, Yan- Xing; Zhao, Qi; Xia, Xiaojun; Wang, Zining
• 署名单位: State Key Lab Oncology South China; Sun Yat Sen University; Tongji University; Sun Yat Sen University; Sun Yat Sen University; Hainan Medical University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13387
• DOI: 10.1073/pnas.2417529122
• 发表日期: 2025-02-04
• 关键词: prc2; chemokines; immunity; protein; ezh2

摘要

Chromobox 2 (CBX2), a crucial component of the polycomb repressive complex (PRC), has been implicated in the development of various human cancers. However, its role in the regulation of tumor immunogenicity and immune evasion remains inadequately understood. In this study, we found that ablation of CBX2 led to tumor growth inhibition, activation of the tumor immune microenvironment, and enhanced therapeutic efficacy of anti- PD1 or adoptive T cell therapies by using murine syngeneic tumor models. By analysis of the CBX2- regulated transcriptional program coupled suppresses interferon signaling independent of its function in the canonical PRC. of HDAC1, which attenuates the H3K27ac modification on the promoter regions of ronment and reduced efficacy of immunotherapy across various human cancer types. in suppression of tumor immunogenicity, thereby presenting a potential target and biomarker for tumor immunotherapy.