MacFeeters-Hamilton Center for Neuro-Oncology Research, Princess Margaret Cancer Center, 14-701, Toronto Medical Discovery Tower (TMDT), 101 College St, Toronto, ON, M5G 1L7, Canada.
Division of Neurosurgery, University Health Network, University of Toronto, Toronto, ON, Canada.
J Neurooncol. 2021 Feb;151(3):443-449. doi: 10.1007/s11060-020-03584-8. Epub 2021 Feb 21.
Meningioma 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.
In 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.
Since 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.
We conclude with a brief review of ongoing clinical trials using checkpoint inhibitors for the treatment of high-grade and refractory meningiomas.
脑膜瘤是最常见的原发性脑肿瘤。大多数脑膜瘤为良性;然而,其中一部分肿瘤具有侵袭性,表现为早期或多次肿瘤复发,对神经外科切除和放疗有抗性。这些患者没有标准的系统治疗方法,由于缺乏对肿瘤进展的准确预测,这些患者的术后管理通常很复杂。
在这篇综述中,我们总结了检查点调节剂的关键免疫抑制作用,包括 PD-1 和 PD-L1 在肿瘤微环境中的相互作用,这导致了针对该轴的努力。
自发现以来,检查点抑制剂已显著改善了许多类型癌症的预后。目前,针对 PD-1 和 PD-L1 蛋白的靶向治疗正在针对脑肿瘤(如胶质母细胞瘤)的几项正在进行的临床试验中进行测试。最近,有一些报告表明,高级别(WHO 分级 II 和 III)脑膜瘤中 PD-L1 表达增加。正在进行几项临床试验,以评估检查点抑制剂在治疗侵袭性脑膜瘤患者中的疗效。在这里,我们回顾了脑膜瘤中的免疫抑制微环境,然后重点关注 PD-L1 表达的临床和病理特征以及肿瘤异质性,以及评估脑膜瘤中 PD-L1 表达的相关挑战。
我们简要回顾了使用检查点抑制剂治疗高级别和难治性脑膜瘤的正在进行的临床试验。