Immunity (Cambridge, Mass.), 2014-11, Vol.41 (5), p.830-842
2014
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- Autor(en) / Beteiligte
- Titel
- STING-Dependent Cytosolic DNA Sensing Mediates Innate Immune Recognition of Immunogenic Tumors
- Ist Teil von
- Immunity (Cambridge, Mass.), 2014-11, Vol.41 (5), p.830-842
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2014
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1074-7613eISSN: 1097-4180DOI: 10.1016/j.immuni.2014.10.017Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4384884
- Format
- –
- Schlagworte
- 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