PD-L1-Mediated Immunosuppression in Glioblastoma Is Associated With the Infiltration and M2-Polarization of Tumor-Associated Macrophages

Abstract

There has been no significant improvements for immune checkpoint inhibitors since its first use. Tumour-associated macrophages (TAMs) are critical mediators in the PD-1/PD-L1 axis, contributing to the immunosuppressive tumour microenvironment. This study aims to investigate the potential role of PD-L1 in regulating TAMs in glioblastoma. Gene expression data and clinical information of glioma patients were collected from TCGA (n = 614) and CGGA (n = 325) databases. Differentially expressed genes between PD-L1^high and PD-L1^low groups were identified and subjected to bioinformatical analysis. We found that PD-L1 was frequently expressed in gliomas with a grade-dependent pattern. Higher PD-L1 expression predicted shorter overall survival. Moreover, PD-L1 was positively correlated with immunosuppressive cells (macrophage, neutrophil and immature DC) and negatively correlated with cytocidal immune cells (CD8⁺ T cell and Th1). Importantly, PD-L1 high expression was significantly correlated with M2-polarization of macrophages (M2-TAMs). We conclude that PD-L1 is an unfavourable prognostic marker for patients with glioblastoma; PD-L1-mediated immunosuppression may attribute to the infiltration and M2-polarization of TAMs.