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

Abstract 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 P 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.