Targeting intrinsic RIG-I signaling turns melanoma cells into type I interferon-releasing cellular antitumor vaccines. (3rd April 2019)

• Record Type: Journal Article
• Authors: Bek, Sarah; Stritzke, Florian; Wintges, Alexander; Nedelko, Tatiana; Böhmer, Daniel F.R.; Fischer, Julius C.; Haas, Tobias; Poeck, Hendrik; Heidegger, Simon
• Is Part Of: Oncoimmunology. Volume 8:Number 4(2019)
• Publication Date: 2019-04-03
• Subjects: Immunogenic cell death -- pattern recognition receptors -- nucleic acid receptors -- RIG-I -- anticancer vaccine -- dendritic cells -- tumor immunotherapy -- personalized medicine; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2019.1570779
• Languages: English
• ISSNs: 2162-402X

Abstract

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.