STING-Dependent Cytosolic DNA Sensing Mediates Innate Immune Recognition of Immunogenic Tumors
By Seng-Ryong Woo, M. Fuertes, L. Corrales, S. Spranger, Michael J. Furdyna, M. Leung, Ryan Duggan, Ying Wang, G. Barber, Katherine A. Fitzgerald and 2 more. Immunity, 2014
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SUMMARY 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.
Subfields: Immunology, Infectious Diseases, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/f3cc26b924333711c96e8564816dce3adfcfd97c
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Citations in the corpus
- Mitochondrial DNA in inflammation and immunity (2020, positive): “STING is required for spontaneous CD8 T-cell priming in vivo [119].”
- Dendritic Cells and Cancer Immunity (2016, background): “Although expression of Ifna genes was not examined, Ifnb expression in these models localized to CD11c+ cells within tumors and draining lymph nodes, hinting at the migration of activated cDCs [43].”
- Tumor-residing Batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy (2017, background): “CXCL9 and CXCL10 are also produced by DCs in a STING-dependent fashion (Woo et al., 2014).”
- IDO in the Tumor Microenvironment: Inflammation, Counter-regulation and Tolerance (2016, positive): “Reports that STING impeded growth of immunogenic tumors and mediated therapeutic effects suggest that immunogenic responses to DNA overcame local tolerogenic processes in these models [62, 63].”