Abstract

Glioma is the most common type of primary brain tumors. After standard treatment regimen (surgical section, radiotherapy and chemotherapy), the average survival time remains merely around 14 months for glioblastoma (grade IV glioma). Recent immune therapy targeting to the immune inhibitory checkpoint axis, i.e., programmed cell death protein 1 (PD-1) and its ligand PD-L1 (i.e., CD274 or B7-H1), has achieved breakthrough in many cancers but still not in glioma. PD-L1 is considered a major prognostic biomarker for immune therapy in many cancers, with anti-PD-1 or anti-PD-L1 antibodies being used. However, the expression and subcellular distribution of PD-L1 in glioma cells exhibits great variance in different studies, severely impairing PD-L1's value as therapeutic and prognostic biomarker in glioma. The role of PD-L1 in modulating immune therapy is complicated. In addition, endogenous PD-L1 plays tumorigenic roles in glioma development. In this review, we summarize PD-L1 mRNA expression and protein levels detected by using different methods and antibodies in human glioma tissues in all literatures, and we evaluate the prognostic value of PD-L1 in glioma. We also summarize the relationships between PD-L1 and immune cell infiltration in glioma. The mechanisms regulating PD-L1 expression and the oncogenic roles of endogenous PD-L1 are discussed. Further, the therapeutic results of using anti-PD-1/PD-L1 antibodies or PD-L1 knockdown are summarized and evaluated. In summary, current results support that PD-L1 is not only a prognostic biomarker of immune therapy, but also a potential therapeutic target for glioma.

Highlights

  • Glioma, predominantly derived from glial cells, is the most common type of primary tumors in the human brain

  • We have identified the intracellular interactions between PD-L1 and H-Ras, which further led to Ras/Erk activation, resulting in promoted glioma cell epithelial mesenchymal transition (EMT), migration and invasion

  • In glioma cells from the C57/GL261 orthotopic glioma model, we found that repaglinide significantly reduced PD-L1 expression, which correlates with the increase of tumor infiltrating lymphocytes (TIL) and the increase of survival time of mice (Xiao et al, 2017)

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Summary

Introduction

Predominantly derived from glial cells, is the most common type of primary tumors in the human brain. The predictive markers in PD-1/PD-L1 antibody therapy are mainly the number of cytotoxic T-lymphocytes inside tumor tissues and the expression level of PD-L1 in cancer cells (Chen et al, 2016).

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