Cancer cells transfer damaged mitochondria into immune cells, causing dysfunction and early ageing in T cells, weakening the body’s natural defence against tumours.
February 2025 – Nature
Key takeaways
- Damaged mitochondria sabotage T cells: Cancer cells transfer their own mitochondria containing mutated DNA into tumour-infiltrating T cells, which then develop mitochondrial dysfunction, reduced energy production and increased oxidative stress
- Immune cells age prematurely: Transferred mitochondria trigger accelerated senescence in T cells, characterised by increased inflammatory signalling, impaired memory formation and reduced ability to divide or kill tumour cells
- Mitochondrial hijack undermines immunotherapy: The presence of these mtDNA mutations in tumours correlates with poor outcomes in patients receiving immune checkpoint inhibitors, suggesting mitochondrial transfer plays a role in resistance to treatment
- Blocking the transfer shows therapeutic promise: Inhibiting mitochondrial transfer or its key regulators, such as USP30 or extracellular vesicle release, can restore T cell function and enhance tumour control, pointing to potential new strategies in cancer immunotherapy
Read the article at: Ikeda, Hideki, et al. “Immune evasion through mitochondrial transfer in the tumour microenvironment.” Nature, vol. 638, 2025, pp. 225–233. https://doi.org/10.1038/s41586-024-08439-0.