Irradiated Tumour Cell-Derived Microparticles Upregulate MHC-I Expression in Cancer Cells via DNA Double-Strand Break Repair Pathway

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

doi:10.1016/j.canlet.2024.216898

Irradiated Tumour Cell-Derived Microparticles Upregulate MHC-I Expression in Cancer Cells via DNA Double-Strand Break Repair Pathway

Cancer Lett. 2024 Apr 24:216898. doi: 10.1016/j.canlet.2024.216898. Online ahead of print.

Authors

Suke Deng¹, Jiacheng Wang¹, Yan Hu¹, Yajie Sun¹, Xiao Yang¹, Bin Zhang¹, Yue Deng¹, Wenwen Wei¹, Zhanjie Zhang¹, Lu Wen¹, You Qin¹, Fang Huang¹, Yuhan Sheng¹, Chao Wan², Kunyu Yang³

Affiliations

¹ Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Key Laboratory of Precision Radiation Oncology.
² Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Key Laboratory of Precision Radiation Oncology. Electronic address: wanc@hust.edu.cn.
³ Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Key Laboratory of Precision Radiation Oncology. Electronic address: yangkunyu@hust.edu.cn.

PMID: 38670306
DOI: 10.1016/j.canlet.2024.216898

Abstract

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.

Keywords: DNA repair; double-strand break; microparticle; radiotherapy.