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STING signaling remodels the tumor microenvironment by antagonizing myeloid-derived suppressor cell expansion.


ABSTRACT: Stimulator of interferon genes (STING), a major adaptor protein in antiviral innate immune signaling, is considered as one of the most important regulators of antiviral and antitumor immunity. Although STING agonists are now intensively studied in clinical trials as a new class of adjuvants to boost cancer immunotherapy, the tumor-intrinsic role of the STING pathway in shaping the tumor microenvironment remains controversial. Here, we discovered that STING plays a vital role in regulation of myeloid-derived suppressor cell (MDSC) differentiation and antitumor immunity in Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC). Mechanistic analyses reveal that STING represses NPC-derived MDSC induction by enhancing SOCS1 expression in both tumor cells and MDSCs. SOCS1 physically interacts with STAT3 through its SH2 domain to prevent STAT3 phosphorylation and dimerization, resulting in reduced MDSC induction via inhibition of GM-CSF and IL-6 production. Notably, reduced tumoral STING expression was found to be significantly associated with a poor prognosis for NPC patients. Our findings reveal a novel mechanism linking STING to tumor microenvironmental cytokine production and MDSC induction.

SUBMITTER: Zhang CX 

PROVIDER: S-EPMC6889506 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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STING signaling remodels the tumor microenvironment by antagonizing myeloid-derived suppressor cell expansion.

Zhang Chuan-Xia CX   Ye Shu-Biao SB   Ni Jian-Jiao JJ   Cai Ting-Ting TT   Liu Yi-Na YN   Huang Dai-Jia DJ   Mai Hai-Qiang HQ   Chen Qiu-Yan QY   He Jia J   Zhang Xiao-Shi XS   Zeng Yi-Xin YX   Li Jiang J   Cui Jun J  

Cell death and differentiation 20190228 11


Stimulator of interferon genes (STING), a major adaptor protein in antiviral innate immune signaling, is considered as one of the most important regulators of antiviral and antitumor immunity. Although STING agonists are now intensively studied in clinical trials as a new class of adjuvants to boost cancer immunotherapy, the tumor-intrinsic role of the STING pathway in shaping the tumor microenvironment remains controversial. Here, we discovered that STING plays a vital role in regulation of mye  ...[more]

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