Growing tumors induce a local STING dependent Type I IFN response in dendritic cells.
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.
Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Lisa
L
Andzinski
Institute for Experimental Infection Research, Twincore, Centre for Experimental and Clinical Infection Research, a Joint Venture between the Helmholtz Centre for Infection Research, Braunschweig, and the Hannover Medical School, Germany, Hannover.
Julia
J
Spanier
Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Nadine
N
Kasnitz
Innate Immunity and Infection, Helmholtz Centre for Infection Research, Braunschweig, Germany.|Institute of Medical Microbiology, Otto-von-Guericke-University, Magdeburg, Germany.
Andrea
A
Kröger
Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY.
Lei
L
Jin
Viral Immune Modulation, Helmholtz Centre for Infection Research, Braunschweig, Germany.|Institute of Virology, Hannover Medical School, Hannover, Germany.
Melanie M
MM
Brinkmann
Institute for Experimental Infection Research, Twincore, Centre for Experimental and Clinical Infection Research, a Joint Venture between the Helmholtz Centre for Infection Research, Braunschweig, and the Hannover Medical School, Germany, Hannover.
Ulrich
U
Kalinke
Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.|Institute of Immunology, Hannover Medical School, Hannover, Germany.
Siegfried
S
Weiss
Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.|Translational Oncology, Department of Otorhinolaryngology, University Hospital, University of Duisburg-Essen, Essen, Germany.
Jadwiga
J
Jablonska
Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.|Institute for Experimental Infection Research, Twincore, Centre for Experimental and Clinical Infection Research, a Joint Venture between the Helmholtz Centre for Infection Research, Braunschweig, and the Hannover Medical School, Germany, Hannover.|Institute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany.
Stefan
S
Lienenklaus
D000818:Animals; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D007157:Immunologic Surveillance; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D047368:Tumor Burden; D000099197:STING Protein
D007370:Interferon Type I; D008565:Membrane Proteins; C530855:Sting1 protein, mouse; D000099197:STING Protein