肿瘤细胞治疗研究
英文原题：Targeting the Tumor Immune Ecosystem in Glioblastoma: Challenges and Innovations in Immunotherapy.
胶质母细胞瘤（GBM）是最具侵袭性的原发性脑肿瘤，以预后差和对常规治疗耐药为特征。
胶质母细胞瘤（GBM）是最具侵袭性的原发性脑肿瘤，预后差且对传统治疗耐药。有效治疗的关键障碍在于其高度免疫抑制且异质性显著的肿瘤微环境（TME），该环境协调免疫逃逸并导致治疗失败。肿瘤相关巨噬细胞（TAM），尤其是M2样表型，可维持GBM增殖、血管生成和干细胞样细胞存续。功能异常的T淋巴细胞，特别是调节性T细胞积聚，也会进一步削弱抗肿瘤免疫。NK细胞、树突状细胞、中性粒细胞和髓源性抑制细胞（MDSC）也通过彼此关联但各异的机制参与免疫抑制。尽管免疫疗法在其他恶性肿瘤中取得成功，免疫检查点抑制剂、CAR-T细胞和肿瘤疫苗在GBM中的疗效仍有限，受新抗原负荷低、抗原异质性及免疫细胞浸润不足等因素阻碍。克服这些挑战需要系统理解GBM TME中的免疫调节回路，并在预测性生物标志物指导下开发联合免疫疗法。本综述系统阐明GBM免疫病理中各类免疫组分的作用，并概述新兴治疗策略。
Glioblastoma (GBM) is the most aggressive primary brain tumor, marked by poor prognosis and resistance to conventional therapies. A critical barrier to effective treatment lies in its highly immunosuppressive and heterogeneous tumor microenvironment (TME), which orchestrates immune evasion and therapeutic failure. Tumor-associated macrophages (TAMs), particularly those with an M2-like phenotype, sustain GBM proliferation, angiogenesis, and stem-like cell maintenance. Dysfunctional T lymphocytes-especially the accumulation of regulatory T cells-further attenuate anti-tumor immunity. Natural killer (NK) cells, dendritic cells, neutrophils, and myeloid-derived suppressor cells (MDSCs) also contribute to immune suppression through distinct yet interconnected mechanisms. Despite the success of immunotherapies in other malignancies, immune checkpoint inhibitors, CAR-T cells, and tumor vaccines have yielded limited efficacy in GBM, hindered by low neoantigen burden, antigenic heterogeneity, and poor immune infiltration. Overcoming these challenges requires a systems-level understanding of the immunoregulatory circuits within the GBM TME and the development of combination immunotherapies guided by predictive biomarkers. This review systematically delineates the roles of immune components in GBM immunopathology and outlines the emerging therapeutic strategies.
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