CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
胶质母细胞瘤的下一代免疫治疗生物制剂
英文原题：Next-generation immunotherapy biologics for glioblastoma.
查看英文原题
Next-generation immunotherapy biologics for glioblastoma.
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中文摘要
胶质母细胞瘤（GBM）尽管免疫检查点抑制剂在其他实体瘤中取得了成功，但对其仍 largely 耐药。III 期试验未显示抗 PD-1 单药治疗的生存获益，这可能反映了 GBM 肿瘤微环境中深刻的髓系驱动免疫抑制、低新抗原负荷、瘤内异质性以及适应性耐药。这些挑战推动了下一代免疫治疗生物制剂的开发，旨在重编程肿瘤微环境并克服 GBM 的固有和适应性耐药。本综述综合了免疫治疗生物制剂的进展，包括免疫检查点联合治疗、细胞因子和免疫调节蛋白、过继细胞疗法、疫苗和溶瘤病毒，重点介绍了关键的临床前见解和新兴的临床试验结果。我们得出结论，改进的肿瘤亚型分型和免疫分析对于指导可能实现 GBM 持久临床获益的联合策略至关重要。
展开英文摘要原文
Glioblastoma (GBM) remains largely resistant to immunotherapy despite the success of immune checkpoint inhibitors in other solid tumors. Phase III trials have not demonstrated survival benefit for anti-PD-1 monotherapy, likely reflecting the GBM tumor microenvironment's profound myeloid-driven immunosuppression, low neoantigen burden, intratumoral heterogeneity, and adaptive resistance.
These challenges have driven the development of next-generation immunotherapy biologics designed to reprogram the tumor microenvironment and overcome the innate and adaptive resistance of GBM. This review synthesizes advances in immunotherapy biologics including immune checkpoint combinations, cytokine and immunomodulatory proteins, adoptive cell therapies, vaccines, and oncolytic viruses, highlighting key preclinical insights and emerging clinical trial results.
We conclude that improved tumor subtyping and immune profiling will be crucial to guide combination strategies that may achieve durable clinical benefit in GBM.
论文信息
- 作者
- Schonfeld E、Sjoholm A、Ha J、Liu J、Nageeb G、Annagiri S、Kim L、Choi J
- 第一作者单位
- Stanford University School of Medicine, Stanford University, Stanford, CA, United States.United States
- 通讯作者单位
- Department of Neurosurgery, Stanford University School of Medicine, Stanford University, Stanford, CA, United States.United States
- 文献类型
- 综述
- 期刊
- Frontiers in immunology2026
- 原文标识
- PubMed 41929511 · DOI 10.3389/fimmu.2026.1775093
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