Meningiomas and the tumor microenvironment: expression of PD-L1 and expression of PD-L1 and interferon-gamma in the prognosis

ABSTRACT Introduction: Meningiomas are the most common intracranial tumors in adults. One of the mechanisms used by tumor cells to escape death by immune cells is to interfere with immunological checkpoints, thereby preventing the establishment of adequate immune response. Following this concept, a promising target for an immunomodulatory therapy is blocking programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1 axis), which is known to be crucial for immune escape mechanisms. Interferon-gamma (IFN-γ) is related to PD-L1 expression, produced by activated T cells, and may promote hyper-regulation of PD-L1 expression in tumor cells. Methods: The retrospective cross-sectional cohort study analyzed 93 patients diagnosed with meningioma of different degrees, and immunohistochemical reactions of PD-L1 and IFN-γ proteins were performed. Results: This study did not detect PD-L1 immunoexpression in any of the 93 analyzed cases. The PD-L1 expression in meningioma cells and their potential role in local immunosuppression are not fully established and their indication for anti-PD-L1 therapy as an alternative treatment for meningiomas is still controversial. Conclusion: IFN-γ immunoexpression was related to lower rates of tumor recurrence and longer progression-free survival time; there was also a relationship with the absence of pleomorphism, better differentiation and lower tumor grade for this marker.

摘要
引言：脑膜瘤是成人最常见的颅内肿瘤。肿瘤细胞逃避免疫细胞杀伤的机制之一是干扰免疫检查点，从而阻碍有效免疫应答的建立。基于这一理论，阻断程序性死亡蛋白1（programmed cell death 1, PD-1）/程序性死亡蛋白配体1（programmed cell death ligand 1, PD-L1）轴是一种极具前景的免疫调节治疗靶点，该轴已被证实对免疫逃逸机制至关重要。γ干扰素（Interferon-gamma, IFN-γ）由活化T细胞产生，与PD-L1表达相关，可促进肿瘤细胞中PD-L1表达的异常调控。
方法：本项回顾性横断面队列研究纳入93例确诊为不同级别脑膜瘤的患者，对PD-L1和IFN-γ蛋白进行了免疫组织化学检测。
结果：本研究在全部93例分析病例中均未检测到PD-L1免疫表达。脑膜瘤细胞中PD-L1的表达及其在局部免疫抑制中的潜在作用尚未完全明确，抗PD-L1治疗作为脑膜瘤替代治疗方案的适应证仍存在争议。
结论：IFN-γ免疫表达与较低的肿瘤复发率和更长的无进展生存期相关；该标志物的表达还与无细胞多形性、分化程度更高以及肿瘤级别更低存在关联。