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

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  • Xinyuan Lei

    (Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
    State University of New York at Stony Brook
    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital)

  • Hsinyu Lin

    (Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital)

  • Jieqi Wang

    (Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital)

  • Zhanpeng Ou

    (Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital)

  • Yi Ruan

    (Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital)

  • Ananthan Sadagopan

    (Massachusetts General Hospital, Harvard Medical School
    Massachusetts Institute of Technology)

  • 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
    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital)

  • Baisheng Chen

    (Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University)

  • Qunxing Li

    (Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital)

  • 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
    Breast Tumor Center, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University)

  • Xiaofeng Zhu

    (Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital
    Breast Tumor Center, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University)

  • Xiaoqing Yuan

    (Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital
    Breast Tumor Center, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University)

  • 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
    Markey Cancer Center, the University of Kentucky, College of Medicine)

  • 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
    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital)

  • Xin Xia

    (Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital)

  • 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
    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital)

  • Jinsong Li

    (Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital)

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.

Suggested Citation

  • 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 & Tia, 2022. "Mitochondrial fission induces immunoescape in solid tumors through decreasing MHC-I surface expression," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31417-x
    DOI: 10.1038/s41467-022-31417-x
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    1. Xi Chen & Dimitrios Iliopoulos & Qing Zhang & Qianzi Tang & Matthew B. Greenblatt & Maria Hatziapostolou & Elgene Lim & Wai Leong Tam & Min Ni & Yiwen Chen & Junhua Mai & Haifa Shen & Dorothy Z. Hu & , 2014. "XBP1 promotes triple-negative breast cancer by controlling the HIF1α pathway," Nature, Nature, vol. 508(7494), pages 103-107, April.
    2. Sebastian Kreiter & Mathias Vormehr & Niels van de Roemer & Mustafa Diken & Martin Löwer & Jan Diekmann & Sebastian Boegel & Barbara Schrörs & Fulvia Vascotto & John C. Castle & Arbel D. Tadmor & Step, 2015. "Erratum: Mutant MHC class II epitopes drive therapeutic immune responses to cancer," Nature, Nature, vol. 523(7560), pages 370-370, July.
    3. Sebastian Kreiter & Mathias Vormehr & Niels van de Roemer & Mustafa Diken & Martin Löwer & Jan Diekmann & Sebastian Boegel & Barbara Schrörs & Fulvia Vascotto & John C. Castle & Arbel D. Tadmor & Step, 2015. "Mutant MHC class II epitopes drive therapeutic immune responses to cancer," Nature, Nature, vol. 520(7549), pages 692-696, April.
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