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STING-Dependent Cytosolic DNA Sensing Promotes Radiation-Induced Type I Interferon-Dependent Antitumor Immunity in Immunogenic Tumors.
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- Author(s): Deng, Liufu1,2; Liang, Hua1,2; Xu, Meng3; Yang, Xuanming3; Burnette, Byron1,2; Arina, Ainhoa1,2; Li, Xiao-Dong4; Mauceri, Helena1,2; Beckett, Michael1,2; Darga, Thomas1,2; Huang, Xiaona1; Gajewski, Thomas F.3; Chen, Zhijian J.4,5; Fu, Yang-Xin2,3 ; Weichselbaum, Ralph R.1,2
- Source:
Immunity (10747613). Nov2014, Vol. 41 Issue 5, p843-852. 10p.- Subject Terms:
- Source:
- Additional Information
- Abstract: 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. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of Immunity (10747613) is the property of Cell Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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