Academic Journal
Activated T cell extracellular vesicle DNA transfer enhances antigen presentation and anti-tumor immunity.
| Τίτλος: | Activated T cell extracellular vesicle DNA transfer enhances antigen presentation and anti-tumor immunity. |
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| Συγγραφείς: | Hu, Mengying, Liu, Di-Ao, Wortzel, Inbal, Collier, Paul, Nelson, Theodore M, Foox, Jonathan, Zhong, Guojie, Tobias, Gabriel, Asao, Tetsuhiko, Bojmar, Linda, Kenific, Candia M, Wang, Gang, Caielli, Simone, Wan, Zurong, Qureshy, Sarah, Reed, Max, Piszczatowski, Richard, Ravisankar, Purnima, Brown, Julia A, Xiong, Sihan, Wang, Huajuan, Lauritzen, Pernille, Aylon, Yael, Molina, Henrik, Jarnagin, William R, Oren, Moshe, Stanger, Ben Z, Bui, Jack, Bergers, Gabriele, Noël, Agnès, Grandgenett, Paul M, Hollingsworth, Michael A, Tuveson, David, Boudreau, Nancy, Bromberg, Jacqueline, Kelsen, David, Jones, David R, Santambrogio, Laura, Zeng, Melody Y, Pascual, Virginia, Kim, Han Sang, Mason, Christopher E, Zhang, Haiying, Matei, Irina R, Lyden, David |
| Πηγή: | Cancer Cell, 44 (5), 965 - 982.e12 (2026-05-11) |
| Στοιχεία εκδότη: | Cell Press, 2026. |
| Έτος έκδοσης: | 2026 |
| Θεματικοί όροι: | EV(DNA), acellular immunotherapy, activated T cell-derived EVs, antigen presentation, gene transfer, Granzymes, DNA, Humans, Animals, Mice, Granzymes/metabolism, Immunotherapy/methods, Cell Line, Tumor, Mice, Inbred C57BL, Extracellular Vesicles/immunology, Extracellular Vesicles/metabolism, Extracellular Vesicles/genetics, Antigen Presentation/immunology, Lymphocyte Activation/immunology, T-Lymphocytes/immunology, T-Lymphocytes/metabolism, Neoplasms/immunology, Neoplasms/therapy, Neoplasms/genetics, DNA/immunology, DNA/metabolism, DNA/genetics, EVDNA, Extracellular Vesicles, Immunotherapy, Lymphocyte Activation, Neoplasms, T-Lymphocytes, Oncology, Cancer Research, Human health sciences, Sciences de la santé humaine, Oncologie |
| Περιγραφή: | 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. |
| Τύπος εγγράφου: | journal article http://purl.org/coar/resource_type/c_6501 article peer reviewed |
| Γλώσσα: | English |
| Relation: | https://api.elsevier.com/content/article/PII:S1535610826001777?httpAccept=text/xml; urn:issn:1535-6108; urn:issn:1878-3686 |
| DOI: | 10.1016/j.ccell.2026.03.023 |
| Σύνδεσμος πρόσβασης: | https://orbi.uliege.be/handle/2268/345778 |
| Rights: | open access http://purl.org/coar/access_right/c_abf2 info:eu-repo/semantics/openAccess |
| Αριθμός Καταχώρησης: | edsorb.345778 |
| Βάση Δεδομένων: | ORBi |
| DOI: | 10.1016/j.ccell.2026.03.023 |
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