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| Home > Publications database > Targeting nucleic acid sensors in tumor cells to reprogram biogenesis and RNA cargo of extracellular vesicles for T cell-mediated cancer immunotherapy. |
| Home > Publications database > Targeting nucleic acid sensors in tumor cells to reprogram biogenesis and RNA cargo of extracellular vesicles for T cell-mediated cancer immunotherapy. |
| Journal Article | DKFZ-2023-01789 |
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2023
Elsevier
Maryland Heights, MO
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Please use a persistent id in citations: doi:10.1016/j.xcrm.2023.101171
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 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.
Keyword(s): RIG-I ; RNA ; STING ; cancer immunotherapy ; cancer resistance ; extracellular vesicles ; innate immunity ; nucleic acid receptors ; personalized therapy
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