TY  - JOUR
AU  - Heidegger, Simon
AU  - Stritzke, Florian
AU  - Dahl, Sarah
AU  - Daßler-Plenker, Juliane
AU  - Joachim, Laura
AU  - Buschmann, Dominik
AU  - Fan, Kaiji
AU  - Sauer, Carolin M
AU  - Ludwig, Nils
AU  - Winter, Christof
AU  - Enssle, Stefan
AU  - Li, Suqi
AU  - Perl, Markus
AU  - Görgens, André
AU  - Haas, Tobias
AU  - Orberg, Erik Thiele
AU  - Göttert, Sascha
AU  - Wölfel, Catherine
AU  - Engleitner, Thomas
AU  - Cortés-Ciriano, Isidro
AU  - Rad, Roland
AU  - Herr, Wolfgang
AU  - Giebel, Bernd
AU  - Ruland, Jürgen
AU  - Bassermann, Florian
AU  - Coch, Christoph
AU  - Hartmann, Gunther
AU  - Poeck, Hendrik
TI  - Targeting nucleic acid sensors in tumor cells to reprogram biogenesis and RNA cargo of extracellular vesicles for T cell-mediated cancer immunotherapy.
JO  - Cell reports / Medicine
VL  - 4
IS  - 9
SN  - 2666-3791
CY  - Maryland Heights, MO
PB  - Elsevier
M1  - DKFZ-2023-01789
SP  - 101171
PY  - 2023
N1  - 2023 Sep 19;4(9):101171
AB  - 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.
KW  - RIG-I (Other)
KW  - RNA (Other)
KW  - STING (Other)
KW  - cancer immunotherapy (Other)
KW  - cancer resistance (Other)
KW  - extracellular vesicles (Other)
KW  - innate immunity (Other)
KW  - nucleic acid receptors (Other)
KW  - personalized therapy (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:37657445
DO  - DOI:10.1016/j.xcrm.2023.101171
UR  - https://inrepo02.dkfz.de/record/282500
ER  -