Irradiated tumour cell-derived microparticles upregulate MHC-I expression in cancer cells via DNA double-strand break repair pathway

作者：Suke Deng, Jiacheng Wang, Yan Hu, Yajie Sun, Xiao Yang, Bin Zhang, Yue Deng, Wenwen Wei, Zhanjie Zhang, Lu Wen, You Qin, Fang Huang, Yuhan Sheng, Chao Wan, Kunyu Yang · 发表于：Cancer Letters · 年份：2024 · DOI：10.1016/j.canlet.2024.216898 · 被引用次数：14 · 研究领域：Immune Cell Function and Interaction、Immunotherapy and Immune Responses、Cancer Immunotherapy and Biomarkers

Radiotherapy (RT) is used for over 50 % of cancer patients and can promote adaptive immunity against tumour antigens. However, the underlying mechanisms remain unclear. Here, we discovered that RT induces the release of irradiated tumour cell-derived microparticles (RT-MPs), which significantly upregulate MHC-I expression on the membranes of non-irradiated cells, enhancing the recognition and killing of these cells by T cells. Mechanistically, RT-MPs induce DNA double-strand breaks (DSB) in tumour cells, activating the ATM/ATR/CHK1-mediated DNA repair signalling pathway, and upregulating MHC-I expression. Inhibition of ATM/ATR/CHK1 reversed RT-MP-induced upregulation of MHC-I. Furthermore, phosphorylation of STAT1/3 following the activation of ATM/ATR/CHK1 is indispensable for the DSB-dependent upregulation of MHC-I. Therefore, our findings reveal the role of RT-MP-induced DSBs and the subsequent DNA repair signalling pathway in MHC-I expression and provide mechanistic insights into the regulation of MHC-I expression after DSBs.