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Immunity. 2014 Nov 20;41(5):830-42. doi: 10.1016/j.immuni.2014.10.017. Epub 2014 Nov 5.

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

Author information

1
Department of Pathology, The University of Chicago, 929 E57th Street GCIS W423H, Chicago, IL 60637, USA.
2
Flow Cytometry Core Facility, The University of Chicago, 924 E57th Street r022, Chicago, IL 60637, USA.
3
Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, MC6092, Chicago, IL 60637, USA.
4
Department of Cell Biology, University of Miami, Rosenstiel Medical Science Building, 4th Floor 1600 N.W. 10th Avenue, Miami, FL 33136, USA.
5
Department of Infectious Diseases and Immunology, University of Massachusetts, 364 Plantation Street, LRB, Worcester, MA 01605, USA.
6
Department of Pathology, The University of Chicago, 929 E57th Street GCIS W423H, Chicago, IL 60637, USA; Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, MC6092, Chicago, IL 60637, USA. Electronic address: tgajewsk@medicine.bsd.uchicago.edu.

Erratum in

  • Immunity. 2015 Jan 20;42(1):199.

Abstract

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-? 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-? 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.

PMID:
25517615
PMCID:
PMC4384884
DOI:
10.1016/j.immuni.2014.10.017
[Indexed for MEDLINE]
Free PMC Article

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