Role of GLUT-1 in the Upregulation of PD-L1 Expression After Radiotherapy and Association of PD-L1 with Favourable Overall Survival in Hypopharyngeal Cancer.

Abstract

PurposeThe alteration of tumor immunity after radiotherapy (RT) has been widely studied in recent years. However, the mechanism through which RT mediates tumor immunity and the involvement of glycolysis in this mediation in hypopharyngeal cancer remain unclear. This study investigated whether RT regulates programmed cell death ligand 1(PD-L1) partly via glucose transporter 1(GLUT-1) expression and whether PD-L1 expression predicts overall survival (OS) in patients with hypopharyngeal cancer.MethodsThe expression of PD-L1 and Glut-1, and the numbers of CD4+, CD8+ T cells were detected by immunohistochemical analysis on 47 pre-RT and 25 post-RT specimens of hypopharyngeal cancer. Changes in these indicators before and after RT were compared, and their association with the OS of patients was analyzed. Moreover, we used siRNA-GLUT-1 to inhibit GLUT-1 expression and examined whether GLUT-1 was a key factor involved in the mediation of PD-L1 expression by RT in vitro.ResultsIn the multivariate analysis, patients with higher PD-L1 expression (p=0.037), higher CD4+ T cell infiltration (p=0.016) and earlier clinical stage (p=0.019) had favourable OS. The expression of PD-L1, and the CD4+ and CD8+ T cells was markedly increased following RT. PD-L1 expression was correlated with Glut-1 pre-RT (p=0.002), but not after RT (p=0.051). The expression of PD-L1 in FaDu cells was upregulated after RT, especially at 96h after RT in vitro. However, the expression of PD-L1 in siRNA-GLUT-1 FaDu cells was markedly decreased at 96h after RT compared with that measured in FaDu cells.ConclusionPatients with high PD-L1 expression and CD4+ T cell infiltration may have favourable OS in hypopharyngeal cancer. RT may increase PD-L1 expression and alter tumor immunity. The expression of PD-L1 was correlated with Glut-1, and inhibition of GLUT-1 expression may decrease the expression of PD-L1. GLUT-1 may participate in the alteration of tumor immunity after RT.