Abstract
IntroductionMeningioma is the most common primary brain tumor. Most meningiomas are benign; however, a subset of these tumors can be aggressive, presenting with early or multiple tumor recurrences that are refractory to neurosurgical resection and radiotherapy. There is no standard systemic therapy for these patients, and post-surgical management of these patients is usually complicated due to lack of accurate prediction for tumor progression.MethodsIn this review, we summarise the crucial immunosuppressive role of checkpoint regulators, including PD-1 and PD-L1 interacting in the tumor microenvironment, which has led to efforts aimed at targeting this axis.ResultsSince their discovery, checkpoint inhibitors have significantly improved the outcome in many types of cancers. Currently, targeted therapy for PD-1 and PD-L1 proteins are being tested in several ongoing clinical trials for brain tumors such as glioblastoma. More recently, there have been some reports implicating increased PD-L1 expression in high-grade (WHO grades II and III) meningiomas. Several clinical trials are underway to assess the efficacy of checkpoint inhibitors in the therapeutic management of patients with aggressive meningiomas. Here, we review the immune suppressive microenvironment in meningiomas, and then focus on clinical and pathological characterization and tumor heterogeneity with respect to PD-L1 expression as well as challenges associated with the assessment of PD-L1 expression in meningioma.ConclusionWe conclude with a brief review of ongoing clinical trials using checkpoint inhibitors for the treatment of high-grade and refractory meningiomas.
Highlights
Meningioma is the most common primary brain tumor
We demonstrated the prognostic significance of higher programmed death-ligand 1 (PD-L1) protein expression for worse recurrencefree survival (RFS) independent of WHO grade, the extent of resection, and maximum tumor diameter (Karimi et al, Scientific Reports, submitted, under review)
Immunohistochemical analysis of PD-L1 expression in several tumor types associated with NF-1 and NF-2 gene mutations, including meningioma, schwannoma, and neurofibroma showed a variable degree of positivity across these tumors; they detected PD-L1 expression in 40% of neurofibromin 2/merlin/schwannomin (NF2)-mutated meningiomas [32]
Summary
Meningiomas arise from the arachidonic cap cells of the meninges and comprise the most common primary brain tumors in adults. Immunohistochemical analysis of PD-L1 expression in several tumor types associated with NF-1 and NF-2 gene mutations, including meningioma, schwannoma, and neurofibroma showed a variable degree of positivity across these tumors; they detected PD-L1 expression in 40% of NF2-mutated meningiomas [32] These findings support the hypothesis that somatic genetic alterations in meningioma can potentially affect checkpoint protein expression and can be accounted for in patient stratification in future immunotherapy. The results of the clinical trials investigating checkpoint inhibitors will provide the therapeutic effect of this type of immunotherapy on tumor progression in aggressive meningioma These findings will help us to determine the predictive biomarkers for response to checkpoint therapy in these patients
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