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

414 Citations (Scopus)

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
Pages (from-to)830-842
Number of pages13
JournalImmunity
Volume41
Issue number5
DOIs
StatePublished - Jan 1 2014

Fingerprint

Interferons
DNA
Genes
Neoplasms
GMP synthase (glutamine-hydrolyzing)
Interferon Regulatory Factor-3
Interferon Type I
Tumor Microenvironment
Antigen-Presenting Cells
Immunotherapy
Dendritic Cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Woo, S. R., Fuertes, M. B., Corrales, L., Spranger, S., Furdyna, M. J., Leung, M. Y. K., ... 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

STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. / Woo, Seng Ryong; Fuertes, Mercedes B.; Corrales, Leticia; Spranger, Stefani; Furdyna, Michael J.; Leung, Michael Y K; Duggan, Ryan; Wang, Ying; Barber, Glen N; Fitzgerald, Katherine A.; Alegre, Maria Luisa; Gajewski, Thomas F.

In: Immunity, Vol. 41, No. 5, 01.01.2014, p. 830-842.

Research output: Contribution to journalArticle

Woo, SR, Fuertes, MB, Corrales, L, Spranger, S, Furdyna, MJ, Leung, MYK, Duggan, R, Wang, Y, Barber, GN, Fitzgerald, KA, Alegre, ML & Gajewski, TF 2014, 'STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors', Immunity, vol. 41, no. 5, pp. 830-842. https://doi.org/10.1016/j.immuni.2014.10.017
Woo SR, Fuertes MB, Corrales L, Spranger S, Furdyna MJ, Leung MYK et al. STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity. 2014 Jan 1;41(5):830-842. https://doi.org/10.1016/j.immuni.2014.10.017
Woo, Seng Ryong ; Fuertes, Mercedes B. ; Corrales, Leticia ; Spranger, Stefani ; Furdyna, Michael J. ; Leung, Michael Y K ; Duggan, Ryan ; Wang, Ying ; Barber, Glen N ; Fitzgerald, Katherine A. ; Alegre, Maria Luisa ; Gajewski, Thomas F. / STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. In: Immunity. 2014 ; Vol. 41, No. 5. pp. 830-842.
@article{1a0a4d5619d54a318ab01787d8bbb8ca,
title = "STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors",
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.",
author = "Woo, {Seng Ryong} and Fuertes, {Mercedes B.} and Leticia Corrales and Stefani Spranger and Furdyna, {Michael J.} and Leung, {Michael Y K} and Ryan Duggan and Ying Wang and Barber, {Glen N} and Fitzgerald, {Katherine A.} and Alegre, {Maria Luisa} and Gajewski, {Thomas F.}",
year = "2014",
month = "1",
day = "1",
doi = "10.1016/j.immuni.2014.10.017",
language = "English",
volume = "41",
pages = "830--842",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors

AU - Woo, Seng Ryong

AU - Fuertes, Mercedes B.

AU - Corrales, Leticia

AU - Spranger, Stefani

AU - Furdyna, Michael J.

AU - Leung, Michael Y K

AU - Duggan, Ryan

AU - Wang, Ying

AU - Barber, Glen N

AU - Fitzgerald, Katherine A.

AU - Alegre, Maria Luisa

AU - Gajewski, Thomas F.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84912120595&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84912120595&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2014.10.017

DO - 10.1016/j.immuni.2014.10.017

M3 - Article

C2 - 25517615

AN - SCOPUS:84912120595

VL - 41

SP - 830

EP - 842

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 5

ER -