%0 Journal Article
%A Heidegger, Simon
%A Stritzke, Florian
%A Dahl, Sarah
%A Daßler-Plenker, Juliane
%A Joachim, Laura
%A Buschmann, Dominik
%A Fan, Kaiji
%A Sauer, Carolin M
%A Ludwig, Nils
%A Winter, Christof
%A Enssle, Stefan
%A Li, Suqi
%A Perl, Markus
%A Görgens, André
%A Haas, Tobias
%A Orberg, Erik Thiele
%A Göttert, Sascha
%A Wölfel, Catherine
%A Engleitner, Thomas
%A Cortés-Ciriano, Isidro
%A Rad, Roland
%A Herr, Wolfgang
%A Giebel, Bernd
%A Ruland, Jürgen
%A Bassermann, Florian
%A Coch, Christoph
%A Hartmann, Gunther
%A Poeck, Hendrik
%T Targeting nucleic acid sensors in tumor cells to reprogram biogenesis and RNA cargo of extracellular vesicles for T cell-mediated cancer immunotherapy.
%J Cell reports / Medicine
%V 4
%N 9
%@ 2666-3791
%C Maryland Heights, MO
%I Elsevier
%M DKFZ-2023-01789
%P 101171
%D 2023
%Z 2023 Sep 19;4(9):101171
%X 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 stimulatory 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 'reprogramming' of tumor EVs as a personalized strategy for T cell-mediated cancer immunotherapy.
%K RIG-I (Other)
%K RNA (Other)
%K STING (Other)
%K cancer immunotherapy (Other)
%K cancer resistance (Other)
%K extracellular vesicles (Other)
%K innate immunity (Other)
%K nucleic acid receptors (Other)
%K personalized therapy (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37657445
%R 10.1016/j.xcrm.2023.101171
%U https://inrepo02.dkfz.de/record/282500