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

Cell Death and Differentiation
Chuan-Xia ZhangJun Cui

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.

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Jul 2, 2019·Cell Cycle·Francien Talens, Marcel A T M Van Vugt
Jan 16, 2020·Cancers·Anzhelika KarjalainenMathias Müller
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Sep 28, 2021·The Journal of Investigative Dermatology·Tianxiao XuJun Guo
Nov 3, 2021·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Jia SunWei Mei

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Methods Mentioned

BETA
flow cytometry
ELISA
PCR
co-immunoprecipitation
immunoprecipitation
transfection
X-tile

Software Mentioned

SPSS
CXP
ImageJ
GraphPad Prism
tile

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