Abstract

A large number of studies have shown that programmed death-ligand 1 (PD-L1) is abnormally expressed in gliomas. However, the prognostic significance of PD-L1 expression in glioma patients remains unresolved. Accordingly, we conducted a meta-analysis to determine the prognostic role of high PD-L1 in patients with glioma. Electronic databases were searched to identify studies evaluating PD-L1 expression and overall survival (OS) in these patients. A total of 6 studies (published in 4 articles) that involved 1052 patients were included. Pooled results showed that high PD-L1 expression was associated with worse OS in glioma patients (HR = 1.30, 95% CI: 1.02–1.65, P = 0.032). Further subgroup analysis indicated that high PD-L1 expression in glioblastoma (GBM) was also associated with worse OS (HR = 1.40, 95% CI: 1.03–1.90, P = 0.030). Conversely, in index subgroup analysis, neither PD-L1 protein (HR = 1.43, 95% CI: 0.97–2.10, P = 0.068) nor gene (HR = 1.20, 95% CI: 0.83–1.74, P = 0.322) expression was significantly associated with OS. PD-L1 may represent a promising biomarker that predicts disease progression in patients with glioma or GBM. However, because of our limited sample size, further prospective or retrospective multi-centre, well-designed studies should be performed to verify this result.

Highlights

  • Gliomas are the most common primary central nervous system (CNS) tumour, representing 40% of all brain tumours[1]

  • Eighty-six manuscripts were excluded from the analysis for the following reasons: 9 were duplicate, 22 were reviews or letters, 32 concerned a carcinoma not related to glioma or GBM, and 23 were not related to programmed death-ligand 1 (PD-L1)

  • Parsa et al found that glioma cells lines (SF126, SF210, U87, U251, and U373) with genetic deletions or mutations in phosphatase and tensin homologue (PTEN) had higher PD-L1 protein levels than cells wild-type for PTEN18

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Summary

Introduction

Gliomas are the most common primary central nervous system (CNS) tumour, representing 40% of all brain tumours[1]. Glioblastoma (GBM, glioma grade IV) is the most malignant and aggressive form of primary brain tumour. Despite the use of a standard treatment regimen, including total surgical resection, radiotherapy, and adjuvant chemotherapy, GBM remains a major clinical challenge, with an overall 5-year survival rate of only 9.8%2. Programed death-ligand 1 (PD-L1) is a T cell costimulatory molecule implicated in tumour immune escape mechanisms. Several studies have found that high PD-L1 expression on glioma cells correlates with poor prognosis[9, 10], though not all reports support this conclusion[11, 12]. It would be useful to determine whether PD-L1 expression is associated with the prognosis of glioma patients. We conducted a meta-analysis to evaluate the prognostic role of PD-L1 in patients with glioma. This is the first meta-analysis to quantitatively synthesize information from all previously published studies related to the potential prognostic value of PD-L1 in glioma patients

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