Tumour-infiltrating lymphocytes (TILs) face a barrage of factors in the tumour microenviroment that affect their metabolism and impair their ability to eradicate tumour cells. Investigating the mechanisms behind this dysfunction, Ikeda et al. show that tumour cells transfer mitochondria containing mutated DNA to TILs, which reprogrammes their metabolism and compromises their functions.

Sequencing of mtDNA in TILs after culturing with cancer cells indicated that the native mitochondria in TILs were replaced by cancer cell mitochondria, establishing homoplasmy. Timelapse imaging of TILs labelled with MitoGreen showed the gradual replacement of green TIL mitochondria with red cancer cell-derived mitochondria after co-culture. Mitochondria transfer was also observed in vivo when TILs were isolated from mice bearing tumours labelled with MitoDsRed.