Glioblastoma (GBM) is an aggressive brain tumor characterized by an immunosuppressive tumor microenvironment (TME), which contributes to treatment resistance and disease progression.Background: Tumor-associated macrophages (TAMs), comprising both resident microglia and bone marrow–derived macrophages, play a central role in supporting tumor growth, angiogenesis, and immune evasion. Most TAMs adopt an M2-like immunosuppressive phenotype, making them a promising target for immunomodulatory strategies in GBM.Method: According to PRISMA guidelines, we conducted a systematic literature review and recruited eligible studies focused on therapeutic approaches targeting TAMs in GBM, emphasizing mechanisms of action, efficacy, and challenges. Data extraction focused on therapeutic classes, outcomes, and TAM-related biomarkers.Results: We identified 30 studies meeting the inclusion criteria. These therapies are categorized into three main strategies: inhibition of TAM recruitment, enhancement of TAM-mediated phagocytosis, and reprogramming of TAMs. Combination strategies, including TAM-targeting with checkpoint inhibitors, nanoparticles, and oncolytic viruses, show synergistic effects in preclinical models.Conclusions: Targeting TAMs represents a multifaceted strategy for GBM treatment. Current evidence underscores the need for combination approaches integrating TAM modulation with existing standard-of-care therapies. Clinical translation remains limited due to challenges such as TAM heterogeneity, plasticity, immunosuppressive therapies, and restricted drug delivery across the blood–brain barrier. Future directions should highlight personalized treatments based on detailed TME profiling. Combining TAM-targeted therapies with agents modulating metabolic or immune pathways, and leveraging advanced delivery systems and spatial transcriptomics may improve efficacy.
胶质母细胞瘤（GBM）是一种侵袭性脑肿瘤，其特征是免疫抑制性肿瘤微环境（TME），这导致了治疗抵抗和疾病进展。背景：肿瘤相关巨噬细胞（TAMs）包括常驻小胶质细胞和骨髓来源的巨噬细胞，在支持肿瘤生长、血管生成和免疫逃逸中发挥核心作用。大多数TAMs呈现M2样免疫抑制表型，这使其成为GBM免疫调节策略的一个有前景的靶点。方法：根据PRISMA指南，我们进行了系统的文献综述，纳入了关注GBM中靶向TAMs治疗方法的合格研究，重点分析了作用机制、疗效和挑战。数据提取侧重于治疗类别、结果以及与TAM相关的生物标志物。结果：我们确定了30项符合纳入标准的研究。这些疗法主要分为三大策略：抑制TAM募集、增强TAM介导的吞噬作用以及重编程TAMs。联合策略，包括将靶向TAMs与检查点抑制剂、纳米颗粒和溶瘤病毒相结合，在临床前模型中显示出协同效应。结论：靶向TAMs代表了GBM治疗的一种多层面策略。现有证据强调了将TAM调节与现有标准治疗相结合的联合方法的必要性。由于TAM异质性、可塑性、免疫抑制疗法以及药物跨越血脑屏障递送受限等挑战，临床转化仍然有限。未来方向应强调基于详细TME分析的个体化治疗。将靶向TAMs的疗法与调节代谢或免疫通路的药物相结合，并利用先进的递送系统和空间转录组学，可能会提高疗效。
Targeting Macrophages in Glioblastoma: Current Therapies and Future Directions
肿瘤(癌症)患者之家