放疗通过表皮生长因子受体下游通路上调胶质细胞瘤程序性死亡配体-1。

Radiotherapy Upregulates Programmed Death Ligand-1 through the Pathways Downstream of Epidermal Growth Factor Receptor in Glioma.

机构信息

Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou 213003, China; Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou 213003, China.

Department of Radiation Oncology, The Third Affiliated Hospital of Soochow University, Jiangsu, Changzhou 213003, China.

出版信息

EBioMedicine. 2018 Feb;28:105-113. doi: 10.1016/j.ebiom.2018.01.027. Epub 2018 Jan 31.

BACKGROUND

In the present study, we aimed to investigate the role of epidermal growth factor receptor (EGFR) pathway in the up-regulation of programmed death ligand-1 (PD-L1) caused by radiotherapy (RT).

MATERIALS AND METHODS

Tissue microarrays (TMA) consisting of glioma cancer specimens from 64 patients were used to examine the correlation between PD-L1 and EGFR levels. Furthermore, we performed in vitro experiments to assess the role of EGFR pathway in RT-upregulated PD-L1 expression using human glioma cell lines U87 and U251.

RESULTS

Our data demonstrated that the PD-L1 expression was significantly correlated with EGFR expression in glioma specimens (χ=5.00, P=0.025). The expressions of PD-L1 at the protein and mRNA levels were both significantly up-regulated by RT (P<0.05). The expressions of phosphorylated EGFR and janus kinase 2 (JAK2) were also induced by RT (P<0.05). Besides, inhibition of EGFR pathway could abrogate the RT-triggered PD-L1 up-regulation (P>0.05). The combination of RT with EGFR inhibitor exhibited the same effect on antitumor immune response compared with the combination of RT with PD-L1 neutralizing antibody (Ab).

CONCLUSIONS

RT could up-regulate the PD-L1 expression through the pathways downstream of EGFR in glioma.

背景

在本研究中，我们旨在研究表皮生长因子受体（EGFR）通路在放射治疗（RT）引起程序性死亡配体-1（PD-L1）上调中的作用。

材料和方法

使用包含 64 名患者的脑肿瘤标本的组织微阵列（TMA）来检查 PD-L1 与 EGFR 水平之间的相关性。此外，我们使用人脑胶质瘤细胞系 U87 和 U251 进行体外实验，评估 EGFR 通路在 RT 上调 PD-L1 表达中的作用。

结果

我们的数据表明，PD-L1 表达与脑肿瘤标本中的 EGFR 表达显著相关（χ=5.00，P=0.025）。PD-L1 的蛋白和 mRNA 水平的表达均被 RT 显著上调（P<0.05）。磷酸化 EGFR 和 Janus 激酶 2（JAK2）的表达也被 RT 诱导（P<0.05）。此外，EGFR 通路的抑制可阻断 RT 触发的 PD-L1 上调（P>0.05）。与 RT 与 PD-L1 中和抗体（Ab）联合应用相比，RT 与 EGFR 抑制剂联合应用对肿瘤免疫反应具有相同的作用。