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

SENG-RYONG WOO; MERCEDES BEATRIZ FUERTES; LETICIA CORRALES; STEFANI SPRANGER; MICHAEL J. FURDYNA; MICHAEL M.Y. LEUNG; RYAN DUGGAN; YING WANG; GLEN N. BARBER; KATHERINE A. FITZGERALD; MARIA-LUISA ALEGRE; THOMAS F. GAJEWSKI

IMMUNITY

CELL PRESS

Lugar: United States; Año: 2014 vol. 41 p. 830 - 842

1074-7613

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.