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中华脑科疾病与康复杂志(电子版)

中华脑科疾病与康复杂志(电子版) ›› 2025, Vol. 15 ›› Issue (03) : 153 -160. doi: 10.3877/cma.j.issn.2095-123X.2025.03.004

功能神经外科

胶质母细胞瘤免疫治疗挑战与cGAS-STING通路纳米策略研究进展
张传鹏1, 张瑜廉2, 党韩寒3, 何昆1, 陈鹏宇3, 张昀昇1, 张黎2, 于炎冰2,†()   
  1. 1100029　北京，北京大学中日友好临床医学院
    2100029　北京，中日友好医院神经外科
    3100730　北京，中国医学科学院北京协和医学院
  • 收稿日期:2025-03-11 出版日期:2025-06-15
  • 通信作者: 于炎冰

Research advances on glioblastoma immunotherapy challenges and cGAS-STING pathway nanostrategies

Chuanpeng Zhang1, Yulian Zhang2, Hanhan Dang3, Kun He1, Pengyu Chen3, Yunsheng Zhang1, Li Zhang2, Yanbing Yu2,†()   

  1. 1Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
    2Department of Neurosurgery, China-Japan Friendship Hospital, Beijing 100029, China
    3Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
  • Received:2025-03-11 Published:2025-06-15
  • Corresponding author: Yanbing Yu
  • Supported by:
    National Key R&D Program of China(2022YFC2402500); National Natural Science Foundation of China(32300816, 32471035); Beijing Natural Science Foundation-Haidian Original Innovation Joint Fund(L222034); Beijing Natural Science Foundation Funded Project(L242112); Elite Medical Professionals Project of China-Japan Friendship Hospital(ZRJY2024-QM07); National High Level Hospital Clinical Research Funding(2022-NHLHCRF-YS-05)
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张传鹏, 张瑜廉, 党韩寒, 何昆, 陈鹏宇, 张昀昇, 张黎, 于炎冰. 胶质母细胞瘤免疫治疗挑战与cGAS-STING通路纳米策略研究进展[J/OL]. 中华脑科疾病与康复杂志(电子版), 2025, 15(03): 153-160.

Chuanpeng Zhang, Yulian Zhang, Hanhan Dang, Kun He, Pengyu Chen, Yunsheng Zhang, Li Zhang, Yanbing Yu. Research advances on glioblastoma immunotherapy challenges and cGAS-STING pathway nanostrategies[J/OL]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2025, 15(03): 153-160.

胶质母细胞瘤（GBM）是中枢神经系统最具侵袭性的恶性肿瘤，其治疗因血脑屏障（BBB）阻隔、肿瘤微环境（TME）的深度免疫抑制及肿瘤异质性而面临巨大挑战，导致现有免疫疗法（如免疫检查点抑制剂）效果有限。这促使研究转向调动先天免疫系统，其中cGAS-STING通路作为胞质DNA的关键感受器和Ⅰ型干扰素（IFN-I）产生的核心枢纽，在激发抗肿瘤免疫中扮演重要角色。然而，GBM常通过STING基因启动子甲基化沉默和胞外环状GMP-AMP降解等机制抑制该通路的活性。近年来，纳米材料作为先进的药物递送系统，为克服这些障碍提供了新的策略。本文系统性地综述了cGAS-STING通路的生物学功能及其在GBM中被抑制的关键因素，并重点评述利用纳米材料跨越BBB、实现STING激动剂的靶向递送、胞内释放及环境响应性调控的研究进展，深入探讨基于纳米技术的STING通路激活策略如何与免疫检查点抑制剂、肿瘤疫苗、放化疗等现有疗法协同，以增强抗肿瘤效果、克服免疫抑制并诱导持久免疫记忆，并总结当前该领域面临的主要挑战（如体内递送效率评估、生物安全性、个体化治疗策略等），旨在为开发更有效的GBM免疫治疗新策略提供参考。

关键词: 胶质母细胞瘤, cGAS-STING通路, 纳米材料, 免疫治疗

Glioblastoma (GBM) remains one of the most aggressive malignancies of the central nervous system. Its treatment faces significant hurdles due to the blood-brain barrier (BBB), the profoundly immunosuppressive tumor microenvironment (TME), and inherent tumor heterogeneity, which limit the efficacy of current immunotherapies, including immune checkpoint inhibitors. This has shifted focus towards harnessing the innate immune system, particularly the cGAS-STING pathway. As a critical sensor of cytosolic DNA and a central hub for type I interferon (IFN-I) production, this pathway plays a vital role in initiating anti-tumor immunity. However, its activity is often suppressed in GBM through mechanisms such as epigenetic silencing of the STING gene promoter and extracellular cyclic GMP-AMP degradation. Recently, nanomaterials have emerged as advanced drug delivery systems offering novel strategies to overcome these obstacles. This review aims to systematically summarize the biological functions of the cGAS-STING pathway, the key factors contributing to its suppression in GBM, and critically evaluates the advancements in utilizing nanomaterials for crossing the BBB, achieving targeted delivery, intracellular release, and environment-responsive regulation of STING agonists. Furthermore, it delves into how nanotechnology-based STING pathway activation strategies can synergize with existing therapies like immune checkpoint blockade, tumor vaccines, radiotherapy, and chemotherapy to enhance anti-tumor efficacy, overcome immunosuppression, and induce durable immune memory. Finally, this review outlines the major challenges currently facing the field (including in vivo delivery assessment, biosafety, and personalized therapeutic approaches), intending to provide insights for the development of more effective immunotherapy strategies against GBM.

Key words: Glioblastoma, cGAS-STING pathway, Nanomaterials, Immunotherapy
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