尽管某些类型癌症的治疗取得了重大进展，但高级别神经胶质瘤（HGG）仍然是一个重大的临床问题。胶质母细胞瘤 (GBM) 是成人中枢神经系统最常见的实体瘤，尽管采用了强化多模式治疗，但诊断后的平均生存时间仅为 15-18 个月。表达嵌合抗原受体（CAR）的 T 细胞已被美国食品和药物管理局批准用于治疗某些血液恶性肿瘤，是一种新的、有前途的治疗选择。然而，由于免疫抑制的肿瘤微环境（TME），CAR-T细胞在实体瘤中的疗效较低。因此，将免疫抑制性 TME 重新编程为促炎表型似乎特别重要，因为它可能会提高 CAR-T 细胞在实体瘤治疗中的有效性。以下文献综述旨在介绍临床前研究的结果，表明通过将 TME 重新编程为促炎表型，可以提高 CAR-T 在 GBM TME 中的疗效。这一目标的实现可能要归功于将 CAR-T 与溶瘤病毒、放射疗法或表观遗传抑制剂相结合进行协同治疗，以及支持 CAR-T 细胞穿过血脑屏障，使受损的血管生成正常化。 TME，通过细胞因子信号传导或通过阻断/敲除T细胞抑制剂来改善CAR-T效应器功能，并调节microRNA表达。在协同治疗中使用以这种方式修饰的 CAR-T 细胞可以通过诱导内源性抗肿瘤反应来延长 HGG 患者的生存期。© 作者，2024。

Despite significant progress in the treatment of some types of cancer, high-grade gliomas (HGGs) remain a significant clinical problem. In the case of glioblastoma (GBM), the most common solid tumor of the central nervous system in adults, the average survival time from diagnosis is only 15-18 months, despite the use of intensive multimodal therapy. Chimeric antigen receptor (CAR)-expressing T cells, which have already been approved by the Food and Drug Administration for use in the treatment of certain hematologic malignancies, are a new, promising therapeutic option. However, the efficacy of CAR-T cells in solid tumors is lower due to the immunosuppressive tumor microenvironment (TME). Reprogramming the immunosuppressive TME toward a pro-inflammatory phenotype therefore seems particularly important because it may allow for increasing the effectiveness of CAR-T cells in the therapy of solid tumors. The following literature review aims to present the results of preclinical studies showing the possibilities of improving the efficacy of CAR-T in the TME of GBM by reprogramming the TME toward a pro-inflammatory phenotype. It may be achievable thanks to the use of CAR-T in a synergistic therapy in combination with oncolytic viruses, radiotherapy, or epigenetic inhibitors, as well as by supporting CAR-T cells crossing of the blood-brain barrier, normalizing impaired angiogenesis in the TME, improving CAR-T effector functions by cytokine signaling or by blocking/knocking out T-cell inhibitors, and modulating the microRNA expression. The use of CAR-T cells modified in this way in synergistic therapy could lead to the longer survival of patients with HGG by inducing an endogenous anti-tumor response.© The Author(s), 2024.