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Antigen presentation

T cell-derived extracellular vesicles promote antitumour immunity through horizontal gene transfer

Nature Reviews Immunology (2026) Cite this article

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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.

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  1. Nature Reviews Immunology http://www.nature.com/nri/

    Kirsty Minton

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  1. Kirsty Minton
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Correspondence to Kirsty Minton.

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Minton, K. T cell-derived extracellular vesicles promote antitumour immunity through horizontal gene transfer. Nat Rev Immunol (2026). https://doi.org/10.1038/s41577-026-01309-y

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