| Title | Activated T cell extracellular vesicle DNA transfer enhances antigen presentation and anti-tumor immunity. |
| Publication Type | Journal Article |
| Year of Publication | 2026 |
| Authors | Hu M, Liu D-A, Wortzel I, Collier P, Nelson TM, Foox J, Zhong G, Tobias G, Asao T, Bojmar L, Kenific CM, Wang G, Caielli S, Wan Z, Qureshy S, Reed M, Piszczatowski R, Ravisankar P, Brown JA, Xiong S, Wang H, Lauritzen P, Aylon Y, Molina H, Jarnagin WR, Oren M, Stanger BZ, Bui J, Bergers G, Noël A, Grandgenett PM, Hollingsworth MA, Tuveson D, Boudreau N, Bromberg J, Kelsen D, Jones DR, Santambrogio L, Zeng MY, Pascual V, Kim HSang, Mason CE, Zhang H, Matei IR, Lyden D |
| Journal | Cancer Cell |
| Date Published | 2026 Apr 30 |
| ISSN | 1878-3686 |
| Abstract | Antigen processing and presentation (APP) is essential for adaptive immunosurveillance. We uncover a mechanism whereby activated T cell-derived extracellular vesicles (ATEVs) drive a positive feedback loop that enhances antigen presentation and immune responses in normal physiology and cancer. ATEV-induced immunogenicity relies on extracellular vesicular double-stranded DNA (EVDNA), which is notably abundant and primarily composed of genomic DNA enriched in immune-related genes, including those encoding APP machinery. Mechanistically, granzyme B (Gzmb) packaged by ATEVs disrupts the nuclear envelope of recipient cells, facilitating intranuclear transfer and subsequent transient expression of EVDNA encoding APP genes. DNase treatment removes most AT-EVDNA, abrogating APP upregulation and thus T cell activation and recruitment to tumors. Notably, ATEVs hold promise as an acellular immunotherapy, restoring APP and synergizing with checkpoint blockade in immunotherapy-refractory tumors. Collectively, our findings uncover a mechanism of transient, non-viral gene delivery by ATEVs that boosts APP and anti-tumor immunity while limiting autoimmunity. |
| DOI | 10.1016/j.ccell.2026.03.023 |
| Custom 1 | |
| Alternate Journal | Cancer Cell |
| PubMed ID | 42066762 |