Akay Faruk, Saleh Maya
Institut National de la Recherche Scientifique (INRS), Centre Armand-Frappier Sante Biotechnologie, Laval, QC, Canada.
Front Immunol. 2025 Jun 26;16:1472710. doi: 10.3389/fimmu.2025.1472710. eCollection 2025.
Glioblastoma (GB) is the most aggressive tumor of the central nervous system (CNS), accounting for almost 80% of all primary brain tumors. Despite standard-of-care consisting of surgical resection, when possible, adjuvant radiotherapy (RT) and chemotherapy with Temozolomide (TMZ), GB remains highly fatal, with an estimated recurrence rate of over 90% and a median overall survival (OS) of around 15 months from diagnosis. Several factors contribute to such poor patient outcome, including a unique myeloid-rich tumor microenvironment (TME) that confers immunosuppression and therapeutic resistance. Multi-omics, single-cell transcriptomics and multi-modal spatial analyses of GB are unraveling the diversity of brain myeloid cells, including activated microglia, border-associated macrophages (BAM), and monocyte-derived glioma-associated macrophages (GAM), instructed by ontogeny, spatial distribution, cell-cell interactions and response to metabolic cues in the TME. In this review, we elaborate on the heterogeneity and plasticity of myeloid cells in GB and discuss the promise and challenges for rational therapeutic targeting of GAMs in GB.
胶质母细胞瘤（GB）是中枢神经系统（CNS）中最具侵袭性的肿瘤，占所有原发性脑肿瘤的近80%。尽管标准治疗方案包括在可能的情况下进行手术切除、辅助放疗（RT）以及使用替莫唑胺（TMZ）进行化疗，但GB仍然具有很高的致死率，估计复发率超过90%，从诊断开始计算的中位总生存期（OS）约为15个月。导致患者预后如此不佳的因素有多个，包括一个独特的富含髓样细胞的肿瘤微环境（TME），该环境会导致免疫抑制和治疗抵抗。对GB进行的多组学、单细胞转录组学和多模态空间分析正在揭示脑髓样细胞的多样性，包括活化的小胶质细胞、边界相关巨噬细胞（BAM）以及单核细胞衍生的胶质瘤相关巨噬细胞（GAM），这些细胞受个体发育、空间分布、细胞间相互作用以及对TME中代谢线索的反应所调控。在这篇综述中，我们详细阐述了GB中髓样细胞的异质性和可塑性，并讨论了针对GB中GAM进行合理治疗靶向的前景与挑战。
