Growing tumors induce a local STING dependent Type I IFN response in dendritic cells. Issue 6 (17th May 2016)

• Record Type: Journal Article
• Authors: Andzinski, Lisa; Spanier, Julia; Kasnitz, Nadine; Kröger, Andrea; Jin, Lei; Brinkmann, Melanie M.; Kalinke, Ulrich; Weiss, Siegfried; Jablonska, Jadwiga; Lienenklaus, Stefan
• Is Part Of: International journal of cancer. Volume 139:Issue 6(2016:Sep. 15)
• Page Start: 1350
• Page End: 1357
• Publication Date: 2016-05-17
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.30159
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : The importance of endogenous Type I IFNs in cancer immune surveillance is well established by now. Their role in polarization of tumor‐associated neutrophilic granulocytes into anti‐tumor effector cells has been recently demonstrated. Yet, the cellular source of Type I IFNs as well as the mode of induction is not clearly defined. Here, we demonstrate that IFN‐β is induced by growing murine tumors. Induction is mainly mediated via STING‐dependent signaling pathways, suggesting tumor derived DNA as trigger. Transcription factors IRF3 and IRF5 were activated under these conditions which is consistent with tumor infiltrating dendritic cells (DCs) being the major cellular source of IFN‐β at the tumor site. Besides DCs, tumor cells themselves are induced to contribute to the production of IFN‐β. Taken together, our data provide further information on immune surveillance by Type I IFNs and suggest novel potent cellular targets for future cancer therapy. Abstract : What's new? Type I interferons (IFNs) are crucial for cancer immune surveillance. However, the source of these molecules during tumor growth has not been well understood. In this study, the authors used an in vivo reporter system to visualize IFN‐β expression. They found that STING and the downstream transcription factors IRF3 and IRF5 are crucial for IFN‐β induction, that tumor‐infiltrating dendritic cells (DCs) and tumor cells themselves are major sources of IFN‐b, and that tumor‐derived DNA may act as a trigger for this induction. These results suggest novel therapeutic targets.