Glioblastoma (GBM) is the most aggressive and lethal primary brain tumor, bearing a survival estimate below 10% at five years, despite standard chemoradiation treatment. At recurrence, systemic treatment options are limited and the standard of care is not well defined, with inclusion in clinical trials being highly encouraged. So far, the use of immunotherapeutic strategies in GBM has not proved to significantly improve patients’ prognosis in the treatment of newly diagnosed GBM, nor in the recurrent setting. Probably this has to do with the unique immune environment of the central nervous system, which harbors several immunosuppressive/pro-tumorigenic factors, both soluble (e.g., TGF-β, IL-10, STAT3, prostaglandin E2, and VEGF) and cellular (e.g., Tregs, M2 phenotype TAMs, and MDSC). Here we review the immune composition of the GBMs microenvironment, specifically focusing on the phenotype and function of the T cell compartment. Moreover, we give hints on the therapeutic strategies, such as immune checkpoint blockade, vaccinations, and adoptive cell therapy, that, interacting with tumor-infiltrating lymphocytes, might both target in different ways the tumor microenvironment and potentiate the activity of standard therapies. The path to be followed in advancing clinical research on immunotherapy for GBM treatment relies on a twofold strategy: testing combinatorial treatments, aiming to restore active immune anti-tumor responses, tackling immunosuppression, and additionally, designing more phase 0 and window opportunity trials with solid translational analyses to gain deeper insight into the on-treatment shaping of the GBM microenvironment.
胶质母细胞瘤（GBM）是最具侵袭性且致死率最高的原发性脑肿瘤，即使接受标准放化疗，其五年生存率仍低于10%。复发时全身性治疗方案有限，标准治疗尚未明确界定，因此强烈建议患者参与临床试验。迄今为止，免疫治疗策略在新诊断或复发性GBM治疗中均未显著改善患者预后。这可能与中枢神经系统独特的免疫微环境有关，该环境存在多种可溶性（如TGF-β、IL-10、STAT3、前列腺素E2和VEGF）及细胞性（如调节性T细胞、M2型肿瘤相关巨噬细胞、髓源性抑制细胞）免疫抑制/促肿瘤因子。本文系统综述GBM微环境的免疫构成，特别聚焦T细胞区室的表型与功能特征。同时探讨以肿瘤浸润淋巴细胞为作用靶点的治疗策略（如免疫检查点阻断、疫苗疗法、过继细胞疗法），这些策略可通过不同方式调控肿瘤微环境并增强标准疗法疗效。推进GBM免疫治疗临床研究需遵循双重路径：一方面测试旨在恢复主动免疫抗肿瘤反应、破解免疫抑制的联合疗法；另一方面设计更多包含实体转化分析的第0期及治疗窗口期试验，以深入解析治疗过程中GBM微环境的重塑机制。
肿瘤(癌症)患者之家