期刊
BMC CANCER
卷 18, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12885-018-4384-8
关键词
PD-L1; CXCR3; CXCL9/10/11; Gastric cancer
类别
资金
- National Natural Science Foundation of China [81602098, 81572374, 81673025, 31770963]
- National Key Research and Development Program of China [2017YFC1308900]
- National Science and Technology Major Project of the Ministry of Science and Technology of China Science [2017ZX09304025]
- Technology Plan Project of Liaoning Province [2014226033, 2016007010]
- General Project of Liaoning province department of education and Distinguished professor of Liaoning Province [LZ2015073, LZ2014037]
Background: 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-gamma 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. Methods: 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. Results: 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. Conclusions: 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.
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