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

Seng Ryong Woo, Mercedes B. Fuertes, Leticia Corrales, Stefani Spranger, Michael J. Furdyna, Michael Y.K. Leung, Ryan Duggan, Ying Wang, Glen N. Barber, Katherine A. Fitzgerald, Maria Luisa Alegre, Thomas F. Gajewski

Research output: Contribution to journalArticle

488 Scopus citations

Abstract

Spontaneous Tcell responses against tumors occur frequently and have prognostic value in patients. The mechanism of innate immune sensing of immunogenic tumors leading to adaptive Tcell responses remains undefined, although type I interferons (IFNs) are implicated in this process. We found that spontaneous CD8+ Tcell 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. Invitro, 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 invivo, 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.

Original languageEnglish (US)
Pages (from-to)830-842
Number of pages13
JournalImmunity
Volume41
Issue number5
DOIs
StatePublished - Nov 20 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors'. Together they form a unique fingerprint.

  • Cite this

    Woo, S. R., Fuertes, M. B., Corrales, L., Spranger, S., Furdyna, M. J., Leung, M. Y. K., Duggan, R., Wang, Y., Barber, G. N., Fitzgerald, K. A., Alegre, M. L., & Gajewski, T. F. (2014). STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity, 41(5), 830-842. https://doi.org/10.1016/j.immuni.2014.10.017