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PD-L1-Mediated Immunosuppression in Glioblastoma Is Associated With the Infiltration and M2-Polarization of Tumor-Associated Macrophages
Frontiers in Immunology ( IF 5.7 ) Pub Date : 2020-10-20 , DOI: 10.3389/fimmu.2020.588552
Zhiyuan Zhu 1, 2 , Hongbo Zhang 1 , Baodong Chen 3 , Xing Liu 4, 5 , Shizhong Zhang 1 , Zhitao Zong 6 , Mengqi Gao 1
Affiliation  

There has been no significant improvements for immune checkpoint inhibitors since its first use. Tumour-associated macrophages (TAMs) are critical mediators in the PD-1/PD-L1 axis, contributing to the immunosuppressive tumour microenvironment. This study aims to investigate the potential role of PD-L1 in regulating TAMs in glioblastoma. Gene expression data and clinical information of glioma patients were collected from TCGA (n = 614) and CGGA (n = 325) databases. Differentially expressed genes between PD-L1high and PD-L1low groups were identified and subjected to bioinformatical analysis. We found that PD-L1 was frequently expressed in gliomas with a grade-dependent pattern. Higher PD-L1 expression predicted shorter overall survival. Moreover, PD-L1 was positively correlated with immunosuppressive cells (macrophage, neutrophil and immature DC) and negatively correlated with cytocidal immune cells (CD8+ T cell and Th1). Importantly, PD-L1 high expression was significantly correlated with M2-polarization of macrophages (M2-TAMs). We conclude that PD-L1 is an unfavourable prognostic marker for patients with glioblastoma; PD-L1-mediated immunosuppression may attribute to the infiltration and M2-polarization of TAMs.



中文翻译:

PD-L1介导的胶质母细胞瘤免疫抑制与肿瘤相关巨噬细胞的浸润和M2极化相关。

自从首次使用以来,免疫检查点抑制剂一直没有明显的改善。肿瘤相关的巨噬细胞(TAM)是PD-1 / PD-L1轴上的关键介质,有助于免疫抑制肿瘤微环境。这项研究旨在调查PD-L1在胶质母细胞瘤中调节TAM的潜在作用。从TCGA(n = 614)和CGGA(n = 325)数据库中收集神经胶质瘤患者的基因表达数据和临床信息。PD-L1和PD-L1之间的差异表达基因确定各组并进行生物信息学分析。我们发现PD-L1经常在神经胶质瘤中以等级依赖的模式表达。较高的PD-L1表达预测较短的总生存期。此外,PD-L1与免疫抑制细胞(巨噬细胞,嗜中性粒细胞和未成熟的DC)呈正相关,与杀细胞免疫细胞(CD8 + T细胞和Th1)呈负相关。重要的是,PD-L1高表达与巨噬细胞(M2-TAM)的M2极化显着相关。我们得出结论,PD-L1是胶质母细胞瘤患者不良的预后指标。PD-L1介导的免疫抑制可能归因于TAM的浸润和M2极化。

更新日期:2020-12-01
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