Immune evasion through mitochondrial transfer in the tumour microenvironment

Cancer cells in the tumour microenvironment use various mechanisms to evade the immune system, particularly T cell attack1. For example, metabolic reprogramming in the tumour microenvironment and mitochondrial dysfunction in tumour-infiltrating lymphocytes (TILs) impair antitumour immune responses2–4. However, detailed mechanisms of such processes remain unclear. Here we analyse clinical specimens and identify mitochondrial DNA (mtDNA) mutations in TILs that are shared with cancer cells. Moreover, mitochondria with mtDNA mutations from cancer cells are able to transfer to TILs. Typically, mitochondria in TILs readily undergo mitophagy through reactive oxygen species. However, mitochondria transferred from…

• BS
  Bristol-Myers Squibb
• EL
  Eli Lilly and Company
• P
  Pfizer
• A
  AstraZeneca
• N
  Nvidia
• SM
  Suzuken Memorial Foundation
• JA
  Japan Agency for Medical Research and Development

  Awards: CREST, JP19cm0106502
• GJ
  GlaxoSmithKline Japan
• KC
  Kowa Company
• TL
  Taiju Life Social Welfare Foundation
• SF
  SGH Foundation
• D
  Daiichi-Sankyo
• IF
  Inamori Foundation
• KM
  Kato Memorial Bioscience Foundation
• KL
  Kowa Life Science Foundation
• AP
  Astellas Pharma
• AF
  Astellas Foundation for Research on Metabolic Disorders
• KF
  Kobayashi Foundation for Cancer Research
• PT
  Princess Takamatsu Cancer Research Fund
• OP
  Ono Pharmaceutical
• NP
  Novartis Pharma
• PJ
  Pfizer Japan
• CP
  Chugai Pharmaceutical
• EL
  Eli Lilly Japan
• JS
  Japan Society for the Promotion of Science

  Award: CREST
• JS
  Japan Science and Technology Agency

  Awards: CREST, JPMJAX2321, JPMJFR2049
• CR
  Core Research for Evolutional Science and Technology
• A
  ACT-X