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胶质瘤中的肠-脑-免疫轴:新兴机制与治疗机遇

英文原题:The Gut-Brain-Immune Axis in Glioma: Emerging Mechanisms and Therapeutic Opportunities.

PubMed 2026/02/12(内容时间) Cell Mol Neurobiol Q1 · IF 7.4(JCR 2025)

研究概要

胶质瘤,尤其是胶质母细胞瘤,是最难治疗的一类癌症,原因在于其高度免疫抑制的肿瘤微环境(TME)以及血脑屏障的限制性。

中文摘要

胶质瘤,尤其是胶质母细胞瘤,因肿瘤微环境(TME)高度免疫抑制及血脑屏障限制,成为最难治疗的癌症之一。近期免疫疗法进展改变了外周肿瘤治疗格局,但在胶质瘤中的成功仍有限。新兴证据提示,肠道微生物组可通过肠—脑—免疫轴显著塑造全身及中枢免疫应答。肠道微生物来源代谢物、免疫细胞调节及神经—免疫信号通路可影响小胶质细胞活化、T细胞浸润,甚至影响免疫检查点抑制剂(ICI)疗效,包括PD-1及TIM-3、LAG-3、TIGIT等新兴靶点。此外,微生物组成也可能影响CAR-T及CAR-NK疗法的效力和持久性,为治疗优化提供新方向。本综述探讨胶质瘤肠—脑—免疫轴的生物学基础,总结关键临床前及临床发现,并重点介绍通过益生菌、工程化微生物或粪菌移植(FMT)调节肠道微生物组、作为免疫治疗辅助策略的潜力。文章还讨论技术和转化挑战,包括个体差异及机制尚不确定。理解肠道与胶质瘤免疫微环境之间动态互作,可能为这一高致死性疾病开辟新的治疗策略并改善结局。

展开英文摘要原文

Gliomas, particularly glioblastomas, represent some of the most treatment-resistant cancers due to their profoundly immunosuppressive tumor microenvironment (TME) and the restrictive nature of the blood brain barrier. While recent advances in immunotherapy have transformed the treatment landscape for peripheral tumors, success in gliomas remains limited. Emerging evidence suggests that the gut microbiota through the gut-brain-immune axis may play a significant role in shaping systemic and central immune responses. Gut-derived microbial metabolites, immune cell modulation, and neuro-immune signaling pathways have been shown to influence microglial activation, T cell infiltration, and even response to immune checkpoint inhibitors (ICIs) such as PD-1 and emerging targets like TIM-3, LAG-3, and TIGIT. Furthermore, the efficacy and persistence of CAR-T and CAR-NK therapies may also be impacted by microbial composition, offering a novel avenue for therapeutic optimization. This review explores the biological underpinnings of the gut-brain-immune axis in glioma, summarizes key preclinical and clinical findings, and highlights the potential of gut microbiota modulation via probiotics, engineered microbes, or fecal microbiota transplantation (FMT) as an adjunct to immunotherapy. We also discuss technical and translational challenges, including interindividual variability and mechanistic uncertainty. Understanding the dynamic crosstalk between the gut and the glioma immune microenvironment may unlock new therapeutic strategies and improve outcomes in this highly lethal disease.

论文信息

作者
Feng R、Yang Z、Zhou Y、Zhao H
第一作者单位
Department of Neurosurgery, The First Affiliated Hospital, Zhejiang University School of Medicine (FAHZU), 79 Qingchun Rd., Shangcheng District, Hangzhou, 330100, Zhejiang, China.China
通讯作者单位
Department of Neurosurgery, the Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266005, Shandong, China. yidao@qdu.edu.cn.China
文献类型
综述
期刊
Cellular and molecular neurobiology2026 Feb 12
原文标识
PubMed 41677988 · DOI 10.1007/s10571-026-01680-3