Mechanism of SOX2 Induced PD-L1 Expression Promoting Immune Escape of Breast Cancer Cells
Objective:To investigate the mechanism of transcription factor sex determining region Y box protein 2(SOX2)gene promoting immune escape of breast cancer cells by inducing the expression of programmed death factor ligand 1(PD-L1).Methods:The expressions of SOX2,PD-L1,T cell immunoglobulin and mucin domain molecule 3(TIM3),and nuclear receptor subfamily 4A group member 1(NR4A1)mRNA and corresponding protein expressions in human breast cancer cell lines MDA-MB-231,SK-BR-3 and nor-mal breast epithelial cell line MCF10A were detected by qRT-PCR,and Western blot.SOX2 knockdown plasmids NC and si-SOX2 were constructed,transfected with MDA-MB-231,and constructed a coculture system with cytokine induced killer cells.They were continu-ously cultured for 48 hours,cell proliferation rate was detected by MTT assay,apoptosis rate was detected by TUNEL assay,T cell killing rate was detected by lactate dehydrogenase(LDH)release assay,T cell activation markers IL-2 and IFN-γ were detected by ELISA,the mRNA expression levels of T cell depletion marker PD-1,TIM3,and NR4A1 were detected by qRT-PCR.Results:Com-pared with MCF10A,the expression levels of SOX2,PD-L1,TIM3,NR4A1 mRNA and corresponding protein expressions in MDA-MB-231 and SK-BR-3 were significantly increased(P＜0.05).Compared with the blank group and NC group,the si-SOX2 group showed significant decrease in the expressions of SOX2 mRNA and PD-L1 protein,significant decrease in cell proliferation rate,increase in cell apoptosis rate,increase in T cell killing rate,increase in IL-2 and IFN-y levels,decrease in the mRNA expression levels of PD-1,TIM3,and NR4A1(P＜0.05).Conclusion:SOX2 gene may enhance the immune escape ability of breast cancer cells by inducing high ex-pression of PD-L1.Silencing SOX2 expression can enhance the lethality of T cells and inhibit tumor proliferation.SOX2 gene is expected to become an important molecular target of breast cancer intervention.
Breast cancerImmune escapeTranscription factor sex determining region Y box protein 2Programmed death factor ligand 1
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