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

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(2) = 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.