STING-dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors

Liufu Deng, Hua Liang, Meng Xu, Xuanming Yang, Byron Burnette, Ainhoa Arina, Xiao Dong Li, Helena Mauceri, Michael Beckett, Thomas Darga, Xiaona Huang, Thomas F. Gajewski, Zhijian J. Chen, Yang Xin Fu, Ralph R. Weichselbaum

Research output: Contribution to journalArticle

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Abstract

Ionizing radiation-mediated tumor regression depends on type I interferon (IFN) and the adaptive immune response, but several pathways control I IFN induction. Here, we demonstrate that adaptor protein STING, but not MyD88, is required for type I IFN-dependent antitumor effects of radiation. In dendritic cells (DCs), STING was required for IFN-β induction in response to irradiated-tumor cells. The cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) mediated sensing of irradiated-tumor cells in DCs. Moreover, STING was essential for radiation-induced adaptive immune responses, which relied on type I IFN signaling on DCs. Exogenous IFN-β treatment rescued the cross-priming bycGAS or STING-deficient DCs. Accordingly, activation of STING by a second messenger cGAMP administration enhanced antitumor immunity induced by radiation. Thus radiation-mediated antitumor immunity in immunogenic tumors requires a functional cytosolic DNA-sensing pathway and suggests that cGAMP treatment might provide a new strategy to improve radiotherapy.

Original languageEnglish (US)
Pages (from-to)543-852
Number of pages310
JournalImmunity
Volume41
Issue number5
DOIs
StatePublished - Nov 20 2014

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Interferon Type I
Dendritic Cells
Immunity
Radiation
Interferons
GMP synthase (glutamine-hydrolyzing)
DNA
Adaptive Immunity
Neoplasms
Cross-Priming
Radiation Effects
Second Messenger Systems
Ionizing Radiation
Radiotherapy
Therapeutics
cyclic guanosine monophosphate-adenosine monophosphate
Proteins

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology
  • Medicine(all)

Cite this

STING-dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors. / Deng, Liufu; Liang, Hua; Xu, Meng; Yang, Xuanming; Burnette, Byron; Arina, Ainhoa; Li, Xiao Dong; Mauceri, Helena; Beckett, Michael; Darga, Thomas; Huang, Xiaona; Gajewski, Thomas F.; Chen, Zhijian J.; Fu, Yang Xin; Weichselbaum, Ralph R.

In: Immunity, Vol. 41, No. 5, 20.11.2014, p. 543-852.

Research output: Contribution to journalArticle

Deng, L, Liang, H, Xu, M, Yang, X, Burnette, B, Arina, A, Li, XD, Mauceri, H, Beckett, M, Darga, T, Huang, X, Gajewski, TF, Chen, ZJ, Fu, YX & Weichselbaum, RR 2014, 'STING-dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors', Immunity, vol. 41, no. 5, pp. 543-852. https://doi.org/10.1016/j.immuni.2014.10.019
Deng, Liufu ; Liang, Hua ; Xu, Meng ; Yang, Xuanming ; Burnette, Byron ; Arina, Ainhoa ; Li, Xiao Dong ; Mauceri, Helena ; Beckett, Michael ; Darga, Thomas ; Huang, Xiaona ; Gajewski, Thomas F. ; Chen, Zhijian J. ; Fu, Yang Xin ; Weichselbaum, Ralph R. / STING-dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors. In: Immunity. 2014 ; Vol. 41, No. 5. pp. 543-852.
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