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转分化现象中的 GSCs:聚焦 CAR-T 疗法

英文原题:GSCs in the Transdifferentiation Phenomenon: Focus on CAR-T-Based Therapy.

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GSCs in the Transdifferentiation Phenomenon: Focus on CAR-T-Based Therapy.

PubMed 2026/02/18(内容时间) Cells Q2 · IF 6(JCR 2025)

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中文摘要

胶质母细胞瘤 (GBM) 仍是最致命的脑肿瘤之一,这在很大程度上归因于胶质母细胞瘤干细胞 (GSCs) 的耐受性和可塑性,它们驱动肿瘤生长、复发以及对常规疗法的耐药。其侵袭性背后的一个关键机制是转分化,即 GSCs 获得内皮细胞样和血管周细胞样表型,促进新生血管形成并重塑肿瘤微环境以维持恶性肿瘤状态。常规治疗往往无法清除这些具有耐受性的细胞群体,凸显了对创新靶向策略的需求。基于嵌合抗原受体 (CAR) 的免疫疗法提供了一种靶向策略,可特异性清除 GSCs,并干扰其在促进肿瘤血管化和抑制免疫反应中的作用。本综述旨在全面概述驱动 GSC 转分化的分子机制,并总结当前为靶向这些细胞而开发的 CAR-T 疗法的概况。通过将 GSC 生物学知识与基于 CAR-T 干预的进展相结合,本工作强调了下一代免疫疗法在克服治疗耐药、限制肿瘤复发和改善 GBM 临床结局方面的潜力。

展开英文摘要原文

Glioblastoma (GBM) remains one of the most lethal brain tumors, largely due to the resilience and plasticity of glioblastoma stem cells (GSCs), which drive tumor growth, recurrence, and resistance to conventional therapies. A key mechanism underlying their aggressiveness is transdifferentiation, whereby GSCs acquire endothelial- and pericyte-like phenotypes, promoting neovascularization and remodeling the tumor microenvironment to sustain malignancy. Conventional treatments often fail to eliminate these resilient populations, highlighting the need for innovative targeted strategies.

Chimeric antigen receptor (CAR)-based immunotherapies offer a targeted strategy to specifically eliminate GSCs and interfere with their role in promoting tumor vascularization and suppressing immune responses. This review aims to provide a comprehensive overview of the molecular mechanisms driving GSC transdifferentiation and to summarize the current landscape of CAR-T therapies developed to target these cells.

By integrating knowledge of GSC biology with advances in CAR-T-based interventions, this work highlights the potential of next-generation immunotherapies to overcome therapeutic resistance, limit tumor recurrence, and improve clinical outcomes in GBM.

论文信息

作者
Di Marco M、Lo Giudice A、Cecala FC、David S、Caruso Bavisotto C、Campanella C、Vitale AM、D'Amico G
单位
Institute of Human Anatomy and Histology, Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90133 Palermo, Italy.Italy
文献类型
综述
期刊
Cells2026 Feb 18
原文标识
PubMed 41744806 · DOI 10.3390/cells15040363