Research ArticleTUMOR IMMUNOLOGY

RIG-I activation is critical for responsiveness to checkpoint blockade

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Science Immunology  13 Sep 2019:
Vol. 4, Issue 39, eaau8943
DOI: 10.1126/sciimmunol.aau8943

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Priming responses to checkpoint blockade

Although activation of intracellular DNA sensing has been proposed as a means to promote antitumor immunity, molecules that regulate sensing of intracellular RNAs have received considerably less attention in this setting. Here, Heidegger et al. report that expression of RNA sensor RIG-I in tumor cells plays a vital role in promoting responsiveness to anti–CTLA-4 therapy in mouse models of cancer. By engineering melanoma cell lines lacking key molecules involved in DNA and RNA sensing, cell death, and type I interferon signaling, the authors have catalogued the relative importance of these pathways in regulating antitumor immunity and responsiveness to checkpoint blockade. The authors propose that activation of RNA sensing could be used to increase the immunogenicity of poorly immunogenic tumors.

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