Gastric cancer mesenchymal stem cells derived IL-8 induces PD-L1 expression in gastric cancer cells via STAT3/mTOR-c-Myc signal axis.
Gastric cancer mesenchymal stem cells derived IL-8 induces PD-L1 expression in gastric cancer cells via STAT3/mTOR-c-Myc signal axis.
复制标题
胃癌间充质干细胞来源的IL-8通过STAT3/mTOR-c-Myc信号轴诱导胃癌细胞中PD-L1的表达。
DOI：
10.1038/s41419-018-0988-9
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发表时间：
2018-09-11
影响因子：
9
通讯作者：
Zhu W
中科院分区：
文献类型：
--
作者：
Sun L;Wang Q;Chen B;Zhao Y;Shen B;Wang H;Xu J;Zhu M;Zhao X;Xu C;Chen Z;Wang M;Xu W;Zhu W
PD-L1在肿瘤细胞中的表达是肿瘤免疫逃逸的主要原因之一。然而，调控胃癌细胞PD-L1表达的确切机制仍不清楚。我们以前的研究表明，间充质干细胞(MSCs)具有广泛的免疫抑制潜能，通过调节天然或获得性免疫系统中的细胞活性来促进肿瘤的发展。本研究旨在研究GCMSCs是否调节GC细胞中PD-L1的表达，并探讨其特定的分子机制。结果表明，GCMSCs增强了GC细胞中PD-L1的表达，从而使GC细胞对CD8+T细胞杀伤产生抵抗。然而，这种耐药性被IL-8抑制而减弱。进一步的研究证明，GCMSCs来源的IL-8通过受STAT3和mTOR信号通路调控的c-Myc诱导GC细胞PD-L1的表达。我们的研究结果表明，阻断GCMSCs来源的IL-8可以克服PD-L1诱导的GC细胞的免疫逃逸，为提高GC的免疫治疗效率提供了一种潜在的策略。
The expression of PD-L1 in tumor cells is one of the main causes of tumor immune escape. However, the exact mechanism for regulating PD-L1 expression in gastric cancer (GC) cells remains unclear. Our previous studies have shown that mesenchymal stem cells (MSCs) exert broad immunosuppressive potential, modulating the activity of cells either in innate or adaptive immune system to promote tumor progress. This study aims to investigate whether GCMSCs regulate the PD-L1 expression in GC cells and explore the specific molecular mechanism. The results have shown that GCMSCs enhanced PD-L1 expression in GC cells resulting in the resistance of GC cells to CD8+ T cells cytotoxicity. However, this resistance was attenuated with IL-8 inhibition. Further studies proved that IL-8 derived from GCMSCs induced PD-L1 expression in GC cells via c-Myc regulated by STAT3 and mTOR signaling pathways. Our data indicated that blocking IL-8 derived from GCMSCs may overcome the immune escape induced by PD-L1 in GC cells and provide a potential strategy to enhance the immunotherapy efficiency in GC.
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