Soltani Amina, Kajtar Bela, Abdelwahab El Husseiny Mohamed Mahmud, Steib Anita, Horvath Zsolt, Mangel Laszlo, Jaromi Luca, Pongracz Judit E
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, University of Pecs, 7624 Pecs, Hungary.
Szentagothai Research Centre, University of Pecs, 7624 Pecs, Hungary.
Pathophysiology. 2021 Jan 8;28(1):34-49. doi: 10.3390/pathophysiology28010004.
In spite of intensive research, the survival rates of patients diagnosed with tumors of the central nervous system (CNS) have not improved significantly in the last decade. Immunotherapy as novel and efficacious treatment option in several other malignancies has failed in neuro-oncology likely due to the immunosuppressive property of the brain tissues. Glioblastoma (GBM) is the most aggressive malignant CNS neoplasm, while meningioma (MNG) is a mainly low grade or benign brain tumor originating from the non-glial tissues of the CNS. The aim of the current preliminary study is to compare the immune microenvironment of MNG and GBM as potential target in immunotherapy. Interestingly, the immune microenvironment of MNG and GBM have proved to be similar. In both tumors types the immune suppressive elements including regulatory T cells (Treg), tumor-associated macrophages (TAM) were highly elevated. The cytokine environment supporting Treg differentiation and the presence of indoleamine 2,3-dioxygenase 1 (IDO1) have also increased the immunosuppressive microenvironment. The results of the present study show an immune suppressive microenvironment in both brain tumor types. In a follow-up study with a larger patient cohort can provide detailed background information on the immune status of individual patients and aid selection of the best immune checkpoint inhibitor or other immune modulatory therapy. Immune modulatory treatments in combination with IDO1 inhibitors might even become alternative therapy for relapsed, multiple and/or malignant MNG or chemo-resistant GBM.
尽管进行了深入研究,但在过去十年中,被诊断患有中枢神经系统(CNS)肿瘤的患者生存率并未显著提高。免疫疗法作为其他几种恶性肿瘤的新型有效治疗选择,在神经肿瘤学中却可能因脑组织的免疫抑制特性而失败。胶质母细胞瘤(GBM)是最具侵袭性的恶性中枢神经系统肿瘤,而脑膜瘤(MNG)是一种主要起源于中枢神经系统非神经胶质组织的低级别或良性脑肿瘤。当前这项初步研究的目的是比较MNG和GBM的免疫微环境,将其作为免疫治疗的潜在靶点。有趣的是,MNG和GBM的免疫微环境已被证明是相似的。在这两种肿瘤类型中,包括调节性T细胞(Treg)、肿瘤相关巨噬细胞(TAM)在内的免疫抑制成分均高度升高。支持Treg分化的细胞因子环境以及吲哚胺2,3-双加氧酶1(IDO1)的存在也增强了免疫抑制微环境。本研究结果显示这两种脑肿瘤类型均存在免疫抑制微环境。在一项针对更大患者队列的后续研究中,可以提供关于个体患者免疫状态的详细背景信息,并有助于选择最佳的免疫检查点抑制剂或其他免疫调节疗法。免疫调节治疗与IDO1抑制剂联合使用甚至可能成为复发性、多发性和/或恶性MNG或化疗耐药GBM的替代疗法。