Radiotherapy Upregulates Programmed Death Ligand-1 through the Pathways Downstream of Epidermal Growth Factor Receptor in Glioma.
Radiotherapy Upregulates Programmed Death Ligand-1 through the Pathways Downstream of Epidermal Growth Factor Receptor in Glioma.
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放射治疗通过胶质瘤表皮生长因子受体下游通路上调程序性死亡配体-1
DOI：
10.1016/j.ebiom.2018.01.027
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发表时间：
2018-03
期刊：
影响因子：
11.1
通讯作者：
Jiang J
中科院分区：
文献类型：
--
作者：
Song X;Shao Y;Jiang T;Ding Y;Xu B;Zheng X;Wang Q;Chen X;Gu W;Wu C;Jiang J
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). 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. Our data demonstrated that the PD-L1 expression was significantly correlated with EGFR expression in glioma specimens (χ2 = 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). RT could up-regulate the PD-L1 expression through the pathways downstream of EGFR in glioma. The PD-L1 expression was significantly correlated with EGFR expression in glioma specimens. RT promoted the phosphorylation of EGFR to activate the JAK2 pathway, which resulted in the upregulation of PD-L1. Inhibition of EGFR pathway could abrogate the RT-triggered PD-L1 up-regulation. Glioma is a highly lethal and common central nervous system tumor with poor 5-year survival rate. It is still urgently necessary to develop more effective therapeutic strategies for glioma. We found radiotherapy up-regulated the PD-L1 expression through the pathways downstream of EGFR in glioma. This finding provides new evidence for the combination of RT with PD-1/PD-L1 or EGFR-TKI inhibitor. That may contribute to the development of new therapeutic strategy for glioma.
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影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
影响因子：
--
作者：
Song X;Shao Y;Gu W;Xu C;Mao H;Pei H;Jiang J
通讯作者：
Jiang J
DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Pardoll DM
通讯作者：
Pardoll DM
影响因子：
3.5
作者：
Lee, SJ;Jang, BC;Choi, IH
通讯作者：
Choi, IH
联合放疗与抗PD-L1抗体协同增强非小细胞肺癌的抗肿瘤作用
影响因子：
20.4
作者：
Gong, Xiaomei;Li, Xuefei;Zhou, Caicun
通讯作者：
Zhou, Caicun