肿瘤细胞治疗研究
英文原题：Breaking immune isolation in glioblastoma.
胶质母细胞瘤（GBM）是典型的免疫冷肿瘤之一，其特征为深度免疫抑制、T细胞排斥、新抗原负荷低以及高度免疫抑制的髓系细胞主导的肿瘤微环境（TME）。
胶质母细胞瘤（GBM）是最典型的免疫冷肿瘤之一，其特征为深度免疫抑制、T细胞排斥、低新抗原负荷以及高度免疫抑制性髓系细胞主导的肿瘤微环境（TME）。尽管免疫治疗取得了进展，包括免疫检查点阻断（ICB）、CAR-T细胞和癌症疫苗，但临床获益仍然有限。本综述综合了旨在将冷TME重编程为免疫活跃状态的多模式策略的新兴证据。我们重点介绍了固有免疫激动剂、溶瘤病毒治疗、精准纳米医学、代谢调节以及放疗-免疫协同作用。我们进一步提出了一个整合框架，结合空间免疫组学、靶向递送技术和TME特异性工程，以克服GBM的治疗瓶颈。
Glioblastoma (GBM) represents one of the prototypical immune-cold tumors, characterized by profound immune suppression, T-cell exclusion, low neoantigen burden, and a highly immunosuppressive myeloid-dominant tumor microenvironment (TME). Despite advances in immunotherapy, including immune checkpoint blockade (ICB), CAR-T cells, and cancer vaccines, clinical benefits remain limited. This review synthesizes emerging evidence on multi-modal strategies aimed at reprogramming the cold TME into an immunologically active state. We highlight innate immune agonists, oncolytic virotherapy, precision nanomedicine, metabolic modulation, and radiotherapy-immune synergies. We further propose an integrated framework combining spatial immunomics, targeted delivery technology, and TME-specific engineering to overcome the therapeutic bottlenecks of GBM.
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