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

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 () and Jinsong Li ()
Additional contact information
Xinyuan Lei: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Hsinyu Lin: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Jieqi Wang: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Zhanpeng Ou: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Yi Ruan: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Ananthan Sadagopan: Massachusetts General Hospital, Harvard Medical School
Weixiong Chen: Longgang District Central Hospital, Affiliated to Guangzhou University of Traditional Chinese Medicine
Shule Xie: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Baisheng Chen: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Qunxing Li: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Jue Wang: Cellular Molecular Diagnostics Center, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Huayue Lin: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital
Xiaofeng Zhu: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital
Xiaoqing Yuan: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital
Tian Tian: Key Laboratory of Human Functional Genomics of Jiangsu, Nanjing Medical University
Xiaobin Lv: Nanchang Key Laboratory of Cancer Pathogenesis and Translational Research, Center Laboratory, the Third Affiliated Hospital, Nanchang University
Sha Fu: Cellular Molecular Diagnostics Center, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Xiaorui Zhu: Yale University of Public Health
Jian Zhou: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Guokai Pan: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Xin Xia: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Bakhos A. Tannous: Massachusetts General Hospital and Harvard Medical School
Soldano Ferrone: Massachusetts General Hospital, Harvard Medical School
Song Fan: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Jinsong Li: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Mitochondrial 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.

Date: 2022
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DOI: 10.1038/s41467-022-31417-x

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