胶质母细胞瘤（GBM）是最具侵袭性的原发性脑癌。这些肿瘤在肿瘤和非肿瘤区室中表现出高度的肿瘤间和肿瘤内异质性、低淋巴细胞浸润和高丰度的骨髓亚群，共同创造了高度促肿瘤发生的免疫抑制微环境。此外，异质GBM细胞浸润邻近的脑组织，重塑神经微环境，促进肿瘤与神经元的电化学耦合以及与非肿瘤性星形胶质细胞的代谢耦合，从而驱动生长。在这里，我们回顾了 GBM 微环境的异质性及其在低级别到高级别胶质瘤转变中的作用，最后讨论了针对肿瘤微环境进行治疗的挑战并概述了未来的研究机会。© 2024 Read 等人；由冷泉港实验室出版社出版。

Glioblastoma (GBM) is the most aggressive primary brain cancer. These tumors exhibit high intertumoral and intratumoral heterogeneity in neoplastic and nonneoplastic compartments, low lymphocyte infiltration, and high abundance of myeloid subsets that together create a highly protumorigenic immunosuppressive microenvironment. Moreover, heterogeneous GBM cells infiltrate adjacent brain tissue, remodeling the neural microenvironment to foster tumor electrochemical coupling with neurons and metabolic coupling with nonneoplastic astrocytes, thereby driving growth. Here, we review heterogeneity in the GBM microenvironment and its role in low-to-high-grade glioma transition, concluding with a discussion of the challenges of therapeutically targeting the tumor microenvironment and outlining future research opportunities.© 2024 Read et al.; Published by Cold Spring Harbor Laboratory Press.