Posttranscriptional Control of PD-L1 Expression by 17β-Estradiol via PI3K/Akt Signaling Pathway in ERα-Positive Cancer Cell Lines.
Posttranscriptional Control of PD-L1 Expression by 17β-Estradiol via PI3K/Akt Signaling Pathway in ERα-Positive Cancer Cell Lines.
复制标题
17β-雌二醇通过ERα阳性癌细胞系中PI3K/AKT信号通路对PD-L1表达的转录后控制。
DOI：
10.1097/igc.0000000000000875
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发表时间：
2017-02
期刊：
影响因子：
--
通讯作者：
You Z
中科院分区：
文献类型：
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作者：
Yang L;Huang F;Mei J;Wang X;Zhang Q;Wang H;Xi M;You Z
Estrogen is a well-known oncogenic driver in endometrial and breast cancers. Programmed cell death protein 1 (PD-1) and its ligands PD-L1 and PD-L2 have been shown to mediate immune evasion of the tumor cells. The purpose of the present study was to assess the effects of estrogen on PD-L1 and PD-L2 expression in endometrial and breast cancer cell lines. 17β-estradiol (E2) -induced expression of PD-L1 and PD-L2 and possible signaling pathway were investigated in endometrial and breast cancer cells. Co-culture of T cells and cancer cells with E2 stimulation was performed to assess the functions of T cells. We found that 17β-estradiol (E2) increased expression of PD-L1, but not PD-L2 protein via activation of phosphoinositide 3-kinase (PI3K)/Akt pathway in Ishikawa and MCF-7 cells. PI3K and Akt inhibitors could block E2's effects. E2 did not increase PD-L1 mRNA transcription, but stabilized PD-L1 mRNA. E2's effects were only observed in estrogen receptor α (ERα) -positive Ishikawa and MCF-7 cells, but not in ERα-negative MDA-MB-231 cells. Co-culture of Ishikawa or MCF-7 cells with T cells inhibited expression of interferon-γ and interleukin-2 and increased Bim expression in the presence of E2. This study provides the first evidence that estrogen up-regulates PD-L1 protein expression in ERα-positive endometrial and breast cancer cells to suppress immune functions of T cells in the tumor microenvironment, demonstrating a new mechanism of how estrogen drives cancer progression.
