Targeting nucleic acid sensors in tumor cells to reprogram biogenesis and RNA cargo of extracellular vesicles for T cell-mediated cancer immunotherapy

Medientyp: E-Artikel

Titel: Targeting nucleic acid sensors in tumor cells to reprogram biogenesis and RNA cargo of extracellular vesicles for T cell-mediated cancer immunotherapy

Beteiligte: Heidegger, Simon [Verfasser:in]; Stritzke, Florian [Verfasser:in]; Dahl, Sarah [Verfasser:in]; Daßler-Plenker, Juliane [Verfasser:in]; Joachim, Laura [Verfasser:in]; Buschmann, Dominik [Verfasser:in]; Fan, Kaiji [Verfasser:in]; Sauer, Carolin M. [Verfasser:in]; Ludwig, Nils [Verfasser:in]; Winter, Christof [Verfasser:in]; Enssle, Stefan [Verfasser:in]; Li, Suqi [Verfasser:in]; Perl, Markus [Verfasser:in]; Görgens, André [Verfasser:in]; Haas, Tobias [Verfasser:in]; Orberg, Erik Thiele [Verfasser:in]; Göttert, Sascha [Verfasser:in]; Wölfel, Catherine [Verfasser:in]; Engleitner, Thomas [Verfasser:in]; Cortés-Ciriano, Isidro [Verfasser:in]; Rad, Roland [Verfasser:in]; Herr, Wolfgang [Verfasser:in]; Giebel, Bernd [Verfasser:in]; Ruland, Jürgen [Verfasser:in]; Bassermann, Florian [Verfasser:in]; Coch, Christoph [Verfasser:in]; Hartmann, Gunther [Verfasser:in]; Poeck, Hendrik [Verfasser:in]

Erschienen: 19 September 2023

Sprache: Englisch

DOI: 10.1016/j.xcrm.2023.101171

Identifikator:

Schlagwörter: cancer immunotherapy ; cancer resistance ; extracellular vesicles ; innate immunity ; nucleic acid receptors ; personalized therapy ; RIG-I ; RNA ; STING

Entstehung:

Anmerkungen: Online verfügbar: 31. August 2023, Artikelversion: 19. September 2023

Beschreibung: 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.

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