[PDF][PDF] STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors

SR Woo, MB Fuertes, L Corrales, S Spranger… - Immunity, 2014 - cell.com
SR Woo, MB Fuertes, L Corrales, S Spranger, MJ Furdyna, MYK Leung, R Duggan, Y Wang…
Immunity, 2014cell.com
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 …
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.
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