文章：

胶质母细胞瘤免疫治疗中靶向肿瘤巨噬细胞区室的基础

The Basis for Targeting the Tumor Macrophage Compartment in Glioblastoma Immunotherapy

原文发布日期：12 May 2025

DOI: 10.3390/cancers17101631

类型: Article

开放获取: 是

英文摘要：

Background:Glioblastoma (GBM) remains the most aggressive primary brain tumor with limited treatment options. The immunosuppressive tumor microenvironment (TME), largely shaped by tumor-associated macrophages (TAMs), represents a significant barrier to effective immunotherapy.Objective:This review aims to explore the role of TAMs within the TME, highlighting the phenotypic plasticity, interactions with tumor cells, and potential therapeutic targets to enhance anti-tumor immunity.Findings:TAMs constitute a substantial portion of the TME, displaying functional plasticity between immunosuppressive and pro-inflammatory phenotypes. Strategies targeting TAMs include depletion, reprogramming, and inhibition of pro-tumor signaling pathways. Preclinical studies show that modifying TAM behavior can shift the TME towards a pro-inflammatory state, enhancing antitumor immune responses. Clinical trials investigating inhibitors of TAM recruitment, polarization, and downstream signaling pathways reveal promising yet limited results, necessitating further research to optimize approaches.Conclusions:Therapeutic strategics targeting TAM plasticity through selective depletion, phenotypic reprogramming, or modulation of downstream immunosuppressive signals represent promising avenues to overcome GBM-associated immunosuppression. Early clinical trials underscore their safety and feasibility, yet achieving meaningful clinical efficacy requires deeper mechanistic understanding and combinatorial approaches integrating macrophage-direct therapies with existing immunotherapeutic modalities.

摘要翻译： 

背景：胶质母细胞瘤（GBM）仍是最具侵袭性的原发性脑肿瘤，治疗手段有限。主要由肿瘤相关巨噬细胞（TAMs）塑造的免疫抑制性肿瘤微环境（TME）是有效免疫治疗的重要障碍。目的：本综述旨在探讨TAMs在TME中的作用，重点阐述其表型可塑性、与肿瘤细胞的相互作用以及增强抗肿瘤免疫的潜在治疗靶点。研究发现：TAMs构成TME的重要组成部分，在免疫抑制与促炎表型之间表现出功能可塑性。针对TAMs的治疗策略包括清除、重编程及抑制促肿瘤信号通路。临床前研究表明，改变TAM行为可将TME转向促炎状态，从而增强抗肿瘤免疫应答。针对TAM募集、极化及下游信号通路抑制剂的临床试验显示出有前景但有限的结果，需要进一步研究以优化治疗方案。结论：通过选择性清除、表型重编程或调节下游免疫抑制信号来靶向TAM可塑性的治疗策略，是克服GBM相关免疫抑制的有效途径。早期临床试验验证了其安全性与可行性，但要实现有意义的临床疗效，仍需更深入的机制理解，并将巨噬细胞导向疗法与现有免疫治疗模式相结合的联合策略。

原文链接：

The Basis for Targeting the Tumor Macrophage Compartment in Glioblastoma Immunotherapy