2. Academic Validation
  3. Mitochondrial fission induces immunoescape in solid tumors through decreasing MHC-I surface expression

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

  • Nat Commun. 2022 Jul 6;13(1):3882. doi: 10.1038/s41467-022-31417-x.
Xinyuan Lei  # 1 2 3,  Hsinyu Lin  # 1 3,  Jieqi Wang  # 1 3,  Zhanpeng Ou  # 1 3,  Yi Ruan 1 3,  Ananthan Sadagopan 4 5,  Weixiong Chen 6,  Shule Xie 1 3,  Baisheng Chen 7,  Qunxing Li 1 3,  Jue Wang 8,  Huayue Lin 3 9,  Xiaofeng Zhu 3 9,  Xiaoqing Yuan 3 9,  Tian Tian 10,  Xiaobin Lv 11 12,  Sha Fu 8,  Xiaorui Zhu 13,  Jian Zhou 14,  Guokai Pan 1 3,  Xin Xia 1 3,  Bakhos A Tannous 15,  Soldano Ferrone 16,  Song Fan 17 18,  Jinsong Li 19 20
Affiliations

Affiliations

  • 1 Department of Oral and Maxillofacial Surgery, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 510120, China.
  • 2 Molecular and Cellular Biology, State University of New York at Stony Brook, Stony Brook, NY, 11794, USA.
  • 3 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital, Guangzhou, 510120, China.
  • 4 Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
  • 5 Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • 6 Department of Stomatology, Longgang District Central Hospital, Affiliated to Guangzhou University of Traditional Chinese Medicine, Shenzhen, 518116, China.
  • 7 Department of Thoracic Surgery, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 510120, China.
  • 8 Cellular Molecular Diagnostics Center, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 510120, China.
  • 9 Breast Tumor Center, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 510120, China.
  • 10 Department of Neurobiology, Key Laboratory of Human Functional Genomics of Jiangsu, Nanjing Medical University, Nanjing, 211166, China.
  • 11 Nanchang Key Laboratory of Cancer Pathogenesis and Translational Research, Center Laboratory, the Third Affiliated Hospital, Nanchang University, Nanchang, 330047, China.
  • 12 Markey Cancer Center, the University of Kentucky, College of Medicine, Lexington, KY, 40506, USA.
  • 13 Department of Chronic Diseases Epidemiology, Yale University of Public Health, New Haven, CT, 06520, USA.
  • 14 Department of Medical Imaging, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
  • 15 Experimental Therapeutics and Molecular Imaging Lab, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02129, USA.
  • 16 Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA. [email protected].
  • 17 Department of Oral and Maxillofacial Surgery, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 510120, China. [email protected].
  • 18 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital, Guangzhou, 510120, China. [email protected].
  • 19 Department of Oral and Maxillofacial Surgery, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 510120, China. [email protected].
  • 20 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation of Sun Yat-Sen Memorial Hospital, Guangzhou, 510120, China. [email protected].
  • # Contributed equally.
PMID: 35794100 DOI: 10.1038/s41467-022-31417-x
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.

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