Heidegger, Simon and Stritzke, Florian and Dahl, Sarah and Dassler-Plenker, Juliane and Joachim, Laura and Buschmann, Dominik and Fan, Kaiji and Sauer, Carolin M. and Ludwig, Nils and Winter, Christof and Enssle, Stefan and Li, Suqi and Perl, Markus and Goergens, Andre and Haas, Tobias and Orberg, Erik Thiele and Goettert, Sascha and Woelfel, Catherine and Engleitner, Thomas and Cortes-Ciriano, Isidro and Rad, Roland and Herr, Wolfgang and Giebel, Bernd and Ruland, Jurgen and Bassermann, Florian and Coch, Christoph and Hartmann, Gunther and Poeck, Hendrik (2023) Targeting nucleic acid sensors in tumor cells to reprogram biogenesis and RNA cargo of extracellular vesicles for T cell-mediated cancer immunotherapy. CELL REPORTS MEDICINE, 4 (9): 101171. ISSN 2666-3791,
Full text not available from this repository. (Request a copy)Abstract
Tumor-derived extracellular vesicles (EVs) have been associated with immune evasion and tumor progression. We show that the RNA-sensing receptor RIG-I within tumor cells governs biogenesis and immunomodulatory function of EVs. Cancer-intrinsic RIG-I activation releases EVs, which mediate dendritic cell maturation and T cell antitumor immunity, synergizing with immune checkpoint blockade. Intact RIG-I, autocrine interferon signaling, and the GTPase Rab27a in tumor cells are required for biogenesis of immunostimulatory EVs. Active intrinsic RIG-I signaling governs composition of the tumor EV RNA cargo including small non-coding stimula-tory RNAs. High transcriptional activity of EV pathway genes and RIG-I in melanoma samples associate with prolonged patient survival and beneficial response to immunotherapy. EVs generated from human melanoma after RIG-I stimulation induce potent antigen-specific T cell responses. We thus define a molecular pathway that can be targeted in tumors to favorably alter EV immunomodulatory function. We propose "reprogram-ming"of tumor EVs as a personalized strategy for T cell-mediated cancer immunotherapy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NF-KAPPA-B; I INTERFERON; RIG-I; DENDRITIC CELLS; RECOGNITION; ACTIVATION; EXOSOMES; REJECTION; IMMUNITY; PROTEIN; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Kieferorthopädie Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Jan 2024 10:02 |
| Last Modified: | 30 Jan 2024 10:02 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60097 |
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