The EGFR pathway is involved in the regulation of PD-L1 expression via the IL-6/JAK/STAT3 signaling pathway in EGFR-mutated non-small cell lung cancer
The EGFR pathway is involved in the regulation of PD-L1 expression via the IL-6/JAK/STAT3 signaling pathway in EGFR-mutated non-small cell lung cancer
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EGFR通路通过IL-6/JAK/STAT3信号通路参与EGFR突变非小细胞肺癌中PD-L1表达的调节
DOI：
10.3892/ijo.2016.3632
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发表时间：
2016-10-01
影响因子：
5.2
通讯作者：
Huang, Jian-An
中科院分区：
文献类型：
--
作者：
Zhang, Nan;Zeng, Yuanyuan;Huang, Jian-An
负调控程序性细胞死亡蛋白1 (PD-1)/程序性死亡配体1 （PD-L1）通路介导的信号，可有效抑制T细胞和B细胞的功能，在免疫应答调节中起关键作用。最近，新出现的证据表明，PD-L1的表达与表皮生长因子受体（EGFR）的突变状态有关。此外，EGFR信号通路的激活可以诱导PD-L1的表达。本研究证实，在非小细胞肺癌（NSCLC）细胞中，活化的EGFR可通过白细胞介素6/Janus激酶/转录激活因子3 （IL-6/JAK/STAT3）信号通路上调PD-L1的表达。表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）处理的细胞可以下调IL-6/JAK/STAT3通路的激活，从而降低PD-L1的表达。此外，在非小细胞肺癌细胞中，PD-Ll表达的沉默与抑制细胞增殖和增强肿瘤细胞凋亡相关。综上所述，我们的研究表明EGFR在NSCLC中通过IL-6/JAK/STAT3信号通路参与调控PD-Ll的表达和细胞增殖。本研究提示靶向治疗与免疫治疗联合治疗非小细胞肺癌的潜力。
Negative regulation of the signal mediated by the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway can effectively inhibit the function of T and B cells, which play a key role in the regulation of immune response. Recently, emerging evidence has suggested that the expression of PD-L1 is related to the mutation status of the epidermal growth factor receptor (EGFR). Moreover, the activation of the EGFR signaling pathway can induce expression of PD-L1. In the present study, we demonstrated that activated EGFR can upregulate the expression of PD-L1 through the interleukin 6/Janus kinase/signal transducer and activator of transcription 3 (IL-6/JAK/STAT3) signaling pathway in non-small cell lung cancer (NSCLC) cells. Cells treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can downregulate the activation of the IL-6/JAK/STAT3 pathway, which subsequently reduces the expression of PD-L1. Furthermore, silencing of PD-Ll expression in NSCLC cells correlated with inhibition of cell proliferation and enhanced tumor cell apoptosis. In summary, our research indicates that EGFR is involved in the regulation of PD-Ll expression and cell proliferation via the IL-6/JAK/STAT3 signaling pathway in NSCLC. The present study suggests the potential of combined targeted therapy with immunotherapy in the treatment of NSCLC.