IFN-γ Promotes Epithelial-Mesenchymal Transition and the Expression of PD-L1 in Pancreatic Cancer
IFN-γ Promotes Epithelial-Mesenchymal Transition and the Expression of PD-L1 in Pancreatic Cancer
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DOI：
10.1016/j.jss.2019.02.038
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发表时间：
2019-08-01
影响因子：
2.2
通讯作者：
Maehara, Yoshihiko
中科院分区：
文献类型：
--
作者：
Imai, Daisuke;Yoshizumi, Tomoharu;Maehara, Yoshihiko
背景：肿瘤免疫反应不仅提供宿主防御，而且加速肿瘤免疫逃逸和表型转换。在此，我们研究了胰腺导管腺癌(PDA)中程序性细胞死亡配体1(PD-L1)的表达与上皮-间充质转化(EMT)相关标记物之间的关系。材料和方法：分析36例胰腺导管腺癌标本中PD-L1、波形蛋白、E-钙粘素和Snail的表达，以及PDA细胞和免疫细胞的浸润情况。结果：免疫组织化学显示波形蛋白与PD-L1表达呈正相关，而双重染色显示两者在PDA细胞中同时表达。Vimentin阳性表达与CD8(+)T细胞数量减少、FoxP3(+)细胞数量增加及患者预后不良有关(P=0.03)。结论：PDA肿瘤细胞PD-L1的表达和EMT与免疫抑制肿瘤微环境密切相关。靶向STAT1联合PD-1/PD-L1免疫治疗可改善PDA患者的预后。(C)2019 Elsevier Inc.保留所有权利。
Background: Tumor immune reactions not only provide host defense but also accelerate tumor immune escape and phenotype switching. Here, we examined the association of programmed cell death ligand 1 (PD-L1) expression with epithelial-mesenchymal transition (EMT)-associated markers in pancreatic ductal adenocarcinoma (PDA) within the context of the tumor microenvironment.Materials and methods: PDA samples from 36 patients were analyzed for PD-L1, vimentin, E-cadherin, and Snail expressions and for PDA cell and immune cell infiltration. PD-L1 expression and EMT in PDA cell lines under conditions of altering interferon gamma (IFN-gamma) signals were also assessed.Results: Immunohistochemistry revealed a significant correlation between vimentin and PD-L1 expression, whereas double staining showed them to be simultaneously expressed by PDA cells. Positive vimentin expression was associated with the infiltration of a lower number of CD8(+) T cells and a higher number of FoxP3(+) cells and poor patient prognosis (P = 0.03). PDA tumor cells promoted PD-L1 expression and EMT under the presence of IFN-gamma, which was inhibited by the signal transducer and activator of transcription(STAT) 1 small interfering RNA.Conclusions: Strong correlations were observed between PD-L1 expression, EMT, and the immunosuppressive tumor microenvironment. Targeting STAT1 combined with PD-1/PD-L1 immunotherapy may improve outcomes for patients with PDA. (C) 2019 Elsevier Inc. All rights reserved.