Format:
25
ISSN:
2666-3791
Content:
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.
Note:
Online verfügbar: 31. August 2023, Artikelversion: 19. September 2023
,
Gesehen am 26.01.2024
In:
Cell reports. Medicine, Cambridge, MA : Cell Press, 2020, 4(2023), 9 vom: Sept., Artikel-ID 101171, Seite 1-25, 2666-3791
In:
volume:4
In:
year:2023
In:
number:9
In:
month:09
In:
elocationid:101171
In:
pages:1-25
In:
extent:25
Language:
English
DOI:
10.1016/j.xcrm.2023.101171
URL:
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