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STING-Dependent Cytosolic DNA Sensing Mediates Innate Immune Recognition of Immunogenic Tumors

Immunity (Cambridge, Mass.), 2014-11, Vol.41 (5), p.830-842 [Peer Reviewed Journal]

2014 Elsevier Inc. ;Copyright © 2014 Elsevier Inc. All rights reserved. ;Copyright Elsevier Limited Nov 20, 2014 ;2014 Elsevier Inc. 2014 ;ISSN: 1074-7613 ;EISSN: 1097-4180 ;DOI: 10.1016/j.immuni.2014.10.017 ;PMID: 25517615

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Title:
STING-Dependent Cytosolic DNA Sensing Mediates Innate Immune Recognition of Immunogenic Tumors
Author: Woo, Seng-Ryong ; Fuertes, Mercedes B. ; Corrales, Leticia ; Spranger, Stefani ; Furdyna, Michael J. ; Leung, Michael Y.K. ; Duggan, Ryan ; Wang, Ying ; Barber, Glen N. ; Fitzgerald, Katherine A. ; Alegre, Maria-Luisa ; Gajewski, Thomas F.
Subjects: Adaptive Immunity ; Adaptor Proteins, Signal Transducing - genetics ; Adoptive Transfer ; Animals ; Antigen-Presenting Cells - cytology ; Antigen-Presenting Cells - immunology ; Antigens ; Cancer ; CD8-Positive T-Lymphocytes - immunology ; Cell Line, Tumor ; Cell Proliferation ; Data analysis ; Defects ; Dendritic Cells - immunology ; Deoxyribonucleic acid ; DNA ; DNA - immunology ; Flow cytometry ; Gene expression ; Immune system ; Immunity, Innate ; Immunotherapy ; Interferon Regulatory Factor-3 - genetics ; Interferon-beta - biosynthesis ; Kinases ; Lymphocyte Activation - immunology ; Lymphocytes ; Melanoma ; Melanoma, Experimental - immunology ; Membrane Proteins - genetics ; Membrane Proteins - immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Differentiation Factor 88 - genetics ; Nucleotidyltransferases ; Peptides ; Proteins ; Receptors, Antigen, T-Cell - immunology ; Receptors, Purinergic P2X7 - genetics ; Software ; Statistical analysis ; Toll-Like Receptor 4 - genetics ; Toll-Like Receptor 9 - genetics ; Tumor Microenvironment - immunology ; Tumors
Is Part Of: Immunity (Cambridge, Mass.), 2014-11, Vol.41 (5), p.830-842
Description: Spontaneous T cell responses against tumors occur frequently and have prognostic value in patients. The mechanism of innate immune sensing of immunogenic tumors leading to adaptive T cell responses remains undefined, although type I interferons (IFNs) are implicated in this process. We found that spontaneous CD8+ T cell priming against tumors was defective in mice lacking stimulator of interferon genes complex (STING), but not other innate signaling pathways, suggesting involvement of a cytosolic DNA sensing pathway. In vitro, IFN-β production and dendritic cell activation were triggered by tumor-cell-derived DNA, via cyclic-GMP-AMP synthase (cGAS), STING, and interferon regulatory factor 3 (IRF3). In the tumor microenvironment in vivo, tumor cell DNA was detected within host antigen-presenting cells, which correlated with STING pathway activation and IFN-β production. Our results demonstrate that a major mechanism for innate immune sensing of cancer occurs via the host STING pathway, with major implications for cancer immunotherapy. [Display omitted] •Spontaneous T cell responses against tumors require the host STING pathway in vivo•Tumor-derived DNA can induce type I interferon production via STING•Tumor DNA can be identified in host APCs in the tumor microenvironment in vivo The tumor-derived factors and host innate immune pathways that activate T cell responses against cancer are unclear. Gajewski and colleagues show a requirement for STING-dependent cytosolic DNA sensing in this process, via a mechanism associated with acquisition of tumor cell DNA by antigen-presenting cells.
Publisher: United States: Elsevier Inc
Language: English
Identifier: ISSN: 1074-7613
EISSN: 1097-4180
DOI: 10.1016/j.immuni.2014.10.017
PMID: 25517615
Source: MEDLINE
Cell Press Archives (Open access)

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STING-Dependent Cytosolic DNA Sensing Mediates Innate Immune Recognition of Immunogenic Tumors

2014 Elsevier Inc. ;Copyright © 2014 Elsevier Inc. All rights reserved. ;Copyright Elsevier Limited Nov 20, 2014 ;2014 Elsevier Inc. 2014 ;ISSN: 1074-7613 ;EISSN: 1097-4180 ;DOI: 10.1016/j.immuni.2014.10.017 ;PMID: 25517615

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