mtDNA transfer from senescent cancer cells to MDSCs promotes immunosuppression

Trends Cancer. 2025 Aug;11(8):716-718. doi: 10.1016/j.trecan.2025.06.010. Epub 2025 Jul 2.

Abstract

Sublethal apoptotic stress causing the permeabilization of some mitochondria coupled with cytosolic mitochondrial DNA (mtDNA) accumulation is known to promote cellular senescence. Lai et al. have recently demonstrated that this may be accompanied by mtDNA release within extracellular vesicles that promote local immunosuppression via myeloid-derived suppressor cells.

Keywords: NF-κB; PD-L1; SASP; STING; VDAC; prostate cancer.

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Cellular Senescence* / genetics
  • Cellular Senescence* / immunology
  • DNA, Mitochondrial* / genetics
  • DNA, Mitochondrial* / metabolism
  • Extracellular Vesicles / metabolism
  • Humans
  • Immune Tolerance*
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Myeloid-Derived Suppressor Cells* / immunology
  • Myeloid-Derived Suppressor Cells* / metabolism
  • Neoplasms* / genetics
  • Neoplasms* / immunology
  • Neoplasms* / pathology

Substances

  • DNA, Mitochondrial