Fu Maowu, Xue Bing, Miao Xiuming, Gao Zong
Department of Neurosurgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
Department of Neurosurgery, Jinan Third People's Hospital, Jinan, Shandong, China.
Front Pharmacol. 2025 Mar 28;16:1584688. doi: 10.3389/fphar.2025.1584688. eCollection 2025.
Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, characterized by rapid proliferation, extensive infiltration, and significant intratumoral heterogeneity. Despite advancements in conventional treatments, including surgery, radiotherapy, and chemotherapy, the prognosis for GBM patients remains poor, with a median survival of approximately 15 months. Immunotherapy has emerged as a promising alternative; however, the unique biological and immunological features, including its immunosuppressive tumor microenvironment (TME) and low mutational burden, render it resistant to many immunotherapeutic strategies. This review explores the key challenges in GBM immunotherapy, focusing on immune evasion mechanisms, the blood-brain barrier (BBB), and the TME. Immune checkpoint inhibitors and CAR-T cells have shown promise in preclinical models but have limited clinical success due to antigen heterogeneity, immune cell exhaustion, and impaired trafficking across the BBB. Emerging strategies, including dual-targeting CAR-T cells, engineered immune cells secreting therapeutic molecules, and advanced delivery systems to overcome the BBB, show potential for enhancing treatment efficacy. Addressing these challenges is crucial for improving GBM immunotherapy outcomes.
胶质母细胞瘤（GBM）是成人中最常见且侵袭性最强的原发性脑肿瘤，其特征为快速增殖、广泛浸润以及显著的肿瘤内异质性。尽管在包括手术、放疗和化疗在内的传统治疗方面取得了进展，但GBM患者的预后仍然很差，中位生存期约为15个月。免疫疗法已成为一种有前景的替代疗法；然而，其独特的生物学和免疫学特征，包括免疫抑制性肿瘤微环境（TME）和低突变负荷，使其对许多免疫治疗策略具有抗性。本综述探讨了GBM免疫治疗中的关键挑战，重点关注免疫逃逸机制、血脑屏障（BBB）和TME。免疫检查点抑制剂和嵌合抗原受体T细胞（CAR-T）在临床前模型中已显示出前景，但由于抗原异质性、免疫细胞耗竭以及跨BBB转运受损，临床成功有限。新兴策略，包括双靶点CAR-T细胞、分泌治疗性分子的工程免疫细胞以及克服BBB的先进递送系统，显示出增强治疗效果的潜力。应对这些挑战对于改善GBM免疫治疗结果至关重要。
