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胶质母细胞瘤的免疫病理学

英文原题:Immunopathology of Glioblastoma.

查看英文原题

Immunopathology of Glioblastoma.

PubMed 2025/10/08(内容时间) Annu Rev Pathol Q1 · IF 34.5(JCR 2025)

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中文摘要

胶质母细胞瘤(GBM)是最常见且恶性程度最高的原发性脑肿瘤,其特征是高度异质且深度免疫抑制的肿瘤微环境(TME),该微环境为肿瘤进展提供了不受约束的环境,并显著增加了治疗干预的复杂性。尽管CAR-T 细胞和免疫检查点抑制剂等免疫治疗手段取得了进展,但由于GBM TME的复杂性和强大的免疫逃逸机制,疗效仍然有限。在本综述中,我们阐明了TME内细胞组分之间导致这种免疫抑制状态的复杂相互作用,包括肿瘤相关巨噬细胞/小胶质细胞、髓源性抑制细胞、调节性T细胞和胶质瘤干细胞,以及导致TME复杂性的其他关键因素,如与中心坏死相关的严重缺氧、血脑屏障和细胞外基质。本综述还重点介绍了免疫逃逸机制和近期免疫治疗方法及其生物学原理,强调了需要同时靶向免疫抑制要素和增强免疫激活的整合治疗策略。

展开英文摘要原文

Glioblastoma (GBM), the most frequent and malignant primary brain tumor, is characterized by a highly diverse and profoundly immunosuppressive tumor microenvironment (TME) that provides an unconstrained environment for tumor progression and significantly complicates therapeutic interventions. Despite advances in immunotherapeutic approaches, such as chimeric antigen receptor T cell and immune checkpoint inhibitors, efficacy remains limited due to the complexity of the GBM TME and robust immune evasion mechanisms.

In this review, we elucidate the intricate interplay among cellular components within the TME that lead to this immunosuppressive state, including tumor-associated macrophages/microglia, myeloid-derived suppressor cells, regulatory T cells, and glioma stem cells, as well as other critical elements that contribute to TME complexity, such as the severe hypoxia associated with central necrosis, the blood-brain barrier, and the extracellular matrix.

This review also highlights mechanisms of immune evasion and recent immunotherapeutic approaches along with their biologic rationale, underscoring the need for integrated therapeutic strategies that both target immunosuppressive elements and enhance immune activation.

论文信息

作者
Li J、Ross JL、Hambardzumyan D、Brat DJ
单位
Department of Pathology, Northwestern Medicine Malnati Brain Tumor Institute of the Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA; email: daniel.brat@northwestern.edu.United States
文献类型
综述
期刊
Annual review of pathology2026 Jan
原文标识
PubMed 41061166 · DOI 10.1146/annurev-pathmechdis-042524-025950