Premium
Growing tumors induce a local STING dependent Type I IFN response in dendritic cells
Author(s) -
Andzinski Lisa,
Spanier Julia,
Kasnitz Nadine,
Kröger Andrea,
Jin Lei,
Brinkmann Melanie M.,
Kalinke Ulrich,
Weiss Siegfried,
Jablonska Jadwiga,
Lienenklaus Stefan
Publication year - 2016
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30159
Subject(s) - immune system , biology , irf3 , cancer research , sting , immunology , effector , dendritic cell , interferon , cytokine , interferon type i , innate immune system , engineering , aerospace engineering
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.