Targeting intrinsic RIG-I signaling turns melanoma cells into type I interferon-releasing cellular antitumor vaccines
Bek S, Stritzke F, Wintges A, Nedelko T, Boehmer DFR, Fischer JC, Haas T, Poeck H, Heidegger S (2019)
Publication Type: Journal article
Publication year: 2019
Journal
Book Volume: 8
Article Number: e1570779
Journal Issue: 4
DOI: 10.1080/2162402X.2019.1570779
Abstract
Resistance to cell death and evasion of immunosurveillance are major causes of cancer persistence and progression. Tumor cell-intrinsic activation of the RNA receptor retinoic acid-inducible gene-I (RIG-I) can trigger an immunogenic form of programmed tumor cell death, but its impact on antitumor responses remains largely unexplored. We show that activation of intrinsic RIG-I signaling induces melanoma cell death that enforces cross-presentation of tumor-associated antigens by bystander dendritic cells. This results in systemic expansion and activation of tumor-antigen specific T cells in vivo with subsequent regression of pre-established melanoma. These processes were dependent on the signaling hub MAVS and type I interferon (IFN-I) signaling in the host cell. Using melanoma cells deficient for the transcription factors IRF3 and IRF7, we demonstrate that RIG-I-activated tumor cells used as a vaccine are a relevant source of IFN-I during T cell cross-priming in vivo. Thus, our findings may facilitate translational development of personalized anticancer vaccines.
Involved external institutions
Technische Universität Dresden
Germany (DE)
Klinikum der Universität München (Großhadern und Innenstadt)
Germany (DE)
Germany (DE)
Klinikum der Universität München (Großhadern und Innenstadt)
Germany (DE)
How to cite
APA:
Bek, S., Stritzke, F., Wintges, A., Nedelko, T., Boehmer, D.F.R., Fischer, J.C.,... Heidegger, S. (2019). Targeting intrinsic RIG-I signaling turns melanoma cells into type I interferon-releasing cellular antitumor vaccines. OncoImmunology, 8(4). https://dx.doi.org/10.1080/2162402X.2019.1570779
MLA:
Bek, Sarah, et al. "Targeting intrinsic RIG-I signaling turns melanoma cells into type I interferon-releasing cellular antitumor vaccines." OncoImmunology 8.4 (2019).
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