The poor immunogenicity of many tumours results in part from their downregulation of the antigen processing and presentation (APP) machinery, including MHC molecules, in both tumour cells and tumour-associated dendritic cells (DCs). Extracellular vesicles (EVs) — membrane-bound nanoparticles released by living cells that contain protein, lipids and nucleic acids — have been shown to facilitate intercellular communication in a range of settings. Hu et al. now show that EVs derived from activated T cells can restore APP in tumour cells and DCs through DNA transfer, thus overcoming immune evasion.

AT-EVs were shown to contain higher levels of DNA than NT-EVs. Whole-genome sequencing indicated that T cell-derived EVDNA is largely of nuclear origin, and pulse-chase experiments showed that it is derived from newly synthesized DNA with genome-wide coverage. DNA from AT-EVs had increased copy number of APP genes compared with DNA from NT-EVs, including entire gene regions with their respective promoters. DNase pre-treatment abolished AT-EV-driven upregulation of APP genes in DCs in vitro, and impaired subsequent allogeneic T cell proliferation, showing that EVDNA is required for the immunostimulatory effects of T cell-derived EVs.