Mitochondrial fission induces immunoescape in solid tumors through decreasing MHC-I surface expression

• DOI: 10.1038/s41467-022-31417-x
• Publication Date: 2022-07-06T08:04:42Z
• Authors: Xinyuan Lei; Hsinyu Lin; Jieqi Wang; Zhanpeng Ou; Yi Ruan; Ananthan Sadagopan; Weixiong Chen; Shule Xie; Baisheng Chen; Qunxing Li; Jue Wang; Huayue Lin; Xiaofeng Zhu; Xiaoqing Yuan; Tian Tian; Xiaobin Lv; Sha Fu; Xiaorui Zhu; Jian Zhou; Guokai Pan; Xin Xia; Bakhos A. Tannous; Soldano Ferrone; Song Fan; Jinsong Li
• Keywords: 0303 health sciences; Science; Q; Protein Serine-Threonine Kinases; Mitochondrial Dynamics; Article; 3. Good health; Major Histocompatibility Complex; Mice; 03 medical and health sciences; Neoplasms; Endoribonucleases; Animals

AbstractMitochondrial dynamics can regulate Major Histocompatibility Complex (MHC)-I antigen expression by cancer cells and their immunogenicity in mice and in patients with malignancies. A crucial role in the mitochondrial fragmentation connection with immunogenicity is played by the IRE1α-XBP-1s axis. XBP-1s is a transcription factor for aminopeptidase TPP2, which inhibits MHC-I complex cell surface expression likely by degrading tumor antigen peptides. Mitochondrial fission inhibition with Mdivi-1 upregulates MHC-I expression on cancer cells and enhances the efficacy of adoptive T cell therapy in patient-derived tumor models. Therefore mitochondrial fission inhibition might provide an approach to enhance the efficacy of T cell-based immunotherapy.