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

L Deng, H Liang, M Xu, X Yang, B Burnette, A Arina… - Immunity, 2014 - cell.com
L Deng, H Liang, M Xu, X Yang, B Burnette, A Arina, XD Li, H Mauceri, M Beckett, T Darga…
Immunity, 2014cell.com
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 …
Summary
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 by cGAS 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.
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