脑胶质瘤微环境研究进展与治疗新策略
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国家自然科学基金 (82192894);北京市医院管理中心“青苗”计划专项(QML20230507); 北京市卫生健康委员会事业发展计划类项目(11000023T000002044300-5)


Advances and novel therapeutic strategies in glioma microenvironment
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    摘要:

    脑胶质瘤是颅内最常见的原发性恶性肿瘤,其中胶质母细胞瘤(GBM)作为侵袭性最强的 原发性脑肿瘤,表现出高度的异质性和异常迅速的增殖能力。由于血脑屏障的存在,传统的手术、放疗 和化疗在治疗 GBM 时效果有限。近年来,免疫疗法作为肿瘤治疗领域的前沿策略,展现了巨大的应用 潜力。然而,GBM所处的免疫抑制微环境及其复杂的免疫逃逸机制,为免疫治疗的实施带来了诸多挑战。 因此,深入研究 GBM 的微环境特征及其与肿瘤细胞的相互作用,成为提升治疗效果的关键。本文综述 了 GBM 微环境中的主要细胞成分,包括肿瘤细胞、免疫细胞及其相互作用以及关键细胞因子在肿瘤进 展中的作用。同时,进一步探讨了新型免疫治疗策略,如嵌合抗原受体 T 细胞(CAR-T)疗法、免疫检查 点抑制剂和其他免疫调节方法,并分析了其在临床应用中面临的挑战与潜在优势。此外,针对微环境 中非肿瘤细胞成分的靶向治疗,如肿瘤相关巨噬细胞(TAMs)和 T 细胞调控,提供了新的研究方向和治 疗思路。全面理解 GBM 免疫微环境的复杂性和动态变化,有助于发现更多有效的治疗靶点,推动个性 化治疗的发展,从而显著提高患者的生存率和生活质量。未来的研究应进一步聚焦于微环境中不同细 胞类型的协同作用及其调控机制,以期开发出更精准、更高效的治疗策略。

    Abstract:

    Gliomas are the most common primary malignant tumors in the intracranial region, among which glioblastoma (GBM), as the most aggressive primary brain tumor, is characterized by high heterogeneity and an abnormally rapid proliferation capacity. Due to the presence of the blood-brain barrier (BBB), traditional treatments such as surgery, radiotherapy, and chemotherapy have limited efficacy in treating GBM. In recent years, immunotherapy has emerged as a cutting-edge strategy in cancer treatment, showing tremendous potential. However, the immunosuppressive microenvironment of GBM and its complex immune evasion mechanisms present significant challenges to the application of immunotherapy. Therefore, in-depth research into the characteristics of the GBM microenvironment and its interactions with tumor cells has become critical for improving therapeutic outcomes.This review focuses on the major cellular components of the GBM microenvironment, including tumor cells, immune cells, and their interactions, as well as the roles of key cytokines in tumor progression. Furthermore, it explores novel immunotherapeutic strategies, such as chimeric antigen receptor T cell (CAR-T) therapy, immune checkpoint inhibitors, and other immunomodulatory approaches, analyzing their challenges and potential advantages in clinical applications. Additionally, it highlights new research directions and therapeutic concepts targeting non-tumor cellular components in the microenvironment, such as the regulation of tumor-associated macrophages (TAMs) and T cells. A comprehensive understanding of the complexity and dynamic changes within the GBM immune microenvironment will facilitate the identification of more effective therapeutic targets, driving the development of personalized treatments and significantly improving patient survival and quality of life. Future research should focus on the synergistic interactions among different cell types within the microenvironment and their regulatory mechanisms to develop more precise and efficient therapeutic strategies.

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周含笑,赵征,江涛.脑胶质瘤微环境研究进展与治疗新策略[J].神经疾病与精神卫生,2025,25(1):2-10
DOI :10.3969/j. issn.1009-6574.2025.01.001.

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  • 在线发布日期: 2025-01-20