CXCL9/10/11, a regulator of PD-L1 expression in gastric cancer.
CXCL9/10/11, a regulator of PD-L1 expression in gastric cancer.
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CXCL9/10/11，胃癌中PD-L1表达的调节因子
DOI：
10.1186/s12885-018-4384-8
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发表时间：
2018-04-24
期刊：
影响因子：
3.8
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Zhang C;Li Z;Xu L;Che X;Wen T;Fan Y;Li C;Wang S;Cheng Y;Wang X;Qu X;Liu Y
程序性死亡配体1（PD-L1）是一种免疫抑制剂，在癌症治疗中发挥重要作用。虽然大多数研究表明PD-L1的表达受细胞内、外调控，IFN-γ是外调控的关键分子，但也有研究提示其他细胞因子在PD-L1的表达中起重要作用。在本研究中，我们研究了胃癌细胞中趋化因子信号通路对PD-L1的调控。采用生物信息学方法对胃癌中PD-L1相关基因进行研究，并提出假说。Western blot法检测胃癌细胞系SGC 7901和MKN 74中PD-L1和CXCR 3的表达。同时，PD-L1和CXCR 3表达的相关性进行了化学评价。此外，在用CXCL 9/10/11处理后检测到PD-L1、pSTAT 3和pAkt。此外，在阻断胃癌7901细胞中的趋化因子信号传导后，评估PD-L1、pSTAT 3和pAkt。基于在线数据库分析，提出CXCL 9/10/11-CXCR 3通过激活STAT和PI 3 K-Akt通路上调PD-L1表达。体外和体内实验证实了这一假设。CXCR 3和PD-L1在胃癌细胞系和组织中均有表达，且两者表达呈正相关。在用CXCL 9/10/11处理后，PD-L1上调，伴随着STAT 3和Akt的活化。在阻断趋化因子信号传导后，PD-L1的上调以及STAT 3和Akt的激活减弱。CXCL 9/10/11-CXCR 3通过激活GC细胞中的STAT和PI 3 K-Akt信号通路上调PD-L1的表达。胃癌组织中PD-L1和CXCR 3的表达呈显著正相关。本文的在线版本（10.1186/s12885-018-4384-8）包含补充材料，可供授权用户使用。
Programmed death-ligand 1 (PD-L1) is an immunosuppressor that plays an important role in cancer treatments. Although majority of the studies demonstrated that PD-L1 expression was regulated by cellular intrinsic and extrinsic controls, and IFN-γ was a key molecule of extrinsic control, other studies imply that other cytokines play important roles in PD-L1 expression. In this study, we investigated the regulation of PD-L1 by chemokine signaling pathway in gastric cancer (GC) cells. Bioinformatics was used to explore the PD-L1-related genes in GC and propose a hypothesis. PD-L1 and CXCR3 expression were detected by western blot in SGC7901 and MKN74 cell lines. Meanwhile, PD-L1 and CXCR3 expressions were immunohistochemically assessed for their relevance. Moreover, PD-L1, pSTAT3 and pAkt were detected after treatment with CXCL9/10/11. Furthermore,PD-L1, pSTAT3 and pAkt were evaluated after blocking chemokine signaling in SGC7901 cells. Based on online database analysis, CXCL9/10/11-CXCR3 is proposed to upregulate PD-L1 expression by activating the STAT and PI3K-Akt pathways. This hypothesis was confirmed by in vitro and vivo experiments. CXCR3 and PD-L1 were expressed in GC cell lines and tissues, and the expression of CXCR3 and PD-L1 was positively related. PD-L1 was upregulated after treatment with CXCL9/10/11, accompanied by activation of STAT3 and Akt. After blocking chemokine signaling, upregulation of PD-L1 and activation of STAT3 and Akt were diminished. CXCL9/10/11-CXCR3 upregulated the expression of PD-L1 by activating the STAT and PI3K-Akt signaling pathways in GC cells. There was a significant positive correlation between the expression of PD-L1 and CXCR3 in gastric cancer patient tissues. The online version of this article (10.1186/s12885-018-4384-8) contains supplementary material, which is available to authorized users.
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