Activation of STAT3 promoting immunosuppressive effect on T cells in MDSCs of breast cancer
10.3969/j.issn.1000-8179.20130108
- VernacularTitle:STAT3磷酸化调控乳腺癌髓系来源抑制细胞介导T细胞免疫抑制的机制研究*
- Author:
Yue WANG
;
Xiubao REN
;
Hui LI
;
Shui CAO
;
Baozhu REN
;
Wenwen YU
;
Peng ZHANG
;
Jing QI
;
Jinpu YU
- Publication Type:Journal Article
- Keywords:
MDSCs;
STAT3;
T cell;
breast cancer
- From:
Chinese Journal of Clinical Oncology
2013;(17):1016-1019
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the status of STAT3 phosphorylation in myeloid-derived suppressor cells (MDSCs) of breast cancer and its function in the immunosuppressive effect of MDSCs on proliferation and cytokine secretion of T cells. Methods:CCD33+cells were isolated from healthy umbilical cord, blood-derived, peripheral blood mononuclear cells and were co-cultured with breast cancer cell line MDA-MB-231 in vitro using Transwell plates to induce MDSCs. The untreated CD33+cells were used as con-trols. Idoxuridine (IDO) suppressor expression and STAT3 phosphorylation were examined using Western blot assay. The proliferation and cytokine secretion of T cells, which were co-cultured with MDSCs, were determined by methyl thiazol tetrazolium assay and en-zyme-linked immunosorbent assay. 1-MT and JSI-124 were used to investigate the function of IDO and pSTAT3 in MDSC-mediated T cell immunosuppression. Results:The protein levels of IDO and pSTAT3 in MDSCs were significantly upregulated. MDSCs obviously suppressed T-cell proliferation, which was reversed by 1-MT or JSI-124 (P<0.05). MDSCs could promote TGF-βand IL-10 secretions, but could also remarkably inhibit IFN-γsecretion (P<0.05). After incubation with 1-MT or JSI-124, the increase in TGF-βand IL-10, as well as the decrease in IFN-γ, was significantly reversed. Conclusion:The upregulated pSTAT3 induced the IDO increase in MDSCs. JSI-124 can block MDSC-mediated immunosuppressive effect on T cells in breast cancer.
