期刊
FRONTIERS IN ONCOLOGY
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2020.00896
关键词
cGAMP; myeloid-derived suppressor cells; metastasis; epithelial-mesenchymal transition; STING
类别
资金
- National Natural Science Foundation of China [21472027, 31270869, 91013001, 31670817]
- National Natural Science Foundation of China-Texas AAMP
- M University International Joint Grant [21411120221]
The role of cGAMP stimulating cGAS-cGAMP-STING-IRF3 pathway to inhibit tumor growth was well-established. Herein, the efficiency and pharmacological mechanism of cGAMP on regulating tumor metastasis was investigated. The effects of cGAMP regulating CD8(+)T cells and myeloid-derived suppressor cells (MDSCs) in tumor microenvironment was explored. In this study, we found that cGAMP boosted STING signaling pathway to activate the production of IFN-gamma from CD8(+)T cells, and decreased the population of MDSCsin vivo. The metastasis in CT26 tumor bearing mice was inhibited by cGAMPviaregulating EMT process. cGAMP played an important role in suppressing the production of reactive oxygen species (ROS) and nitric oxide (NO) from MDSCs, abolished the suppressive function of MDSCs to the T cells. All in all, the results indicated that the STING agonist cGAMP activated the production of IFN-gamma from CD8(+)T cells to suppress MDSCsin vivo.
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