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Glioblastoma-associated macrophages in glioblastoma: from their function and mechanism to therapeutic advances

Cancer Gene Therapy volume 32, pages 595–607 (2025)Cite this article

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Abstract

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor in adults and has high mortality rates worldwide. GBM progression, treatment, and prognosis are influenced by the tumor microenvironment (TME), which includes immune, stromal, and tumor cells. Among them, glioblastoma-associated macrophages (GAMs) act as key regulators of GBM pathobiology. GAMs exhibit remarkable plasticity, as they can exhibit both protumor and antitumor effects. However, their function is determined by polarization and the TME. In this review, we provide a comprehensive overview of the current understanding of the biology of GAMs in GBM, including their origins, phenotypic diversity, and functional roles. We discuss the intricate crosstalk between GAMs and tumor cells, as well as other immune and stromal components, and highlight the mechanisms underlying GAM-mediated tumor progression, invasion, angiogenesis, and immune system evasion. Furthermore, we explore the therapeutic implications of targeting GAMs in GBM and discuss emerging strategies aimed at reprogramming GAMs toward an antitumorigenic phenotype or selectively depleting protumorigenic subsets. The final aim is to develop innovative therapeutic approaches that disrupt GBMs. By leveraging our increased understanding of GAM biology, we lay the foundation for transformative advances in GBM treatment to improve patient prognosis.

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Fig. 1: The role of GAMs in GBM progression.
Fig. 2: Polarization of M1 and M2 GAMs.
Fig. 3: Strategies to target GAMS.

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Funding

This work was supported by the Outstanding Postdoctoral Innovative Talent Project of Hunan Province (No. 2021RC2037) and the Natural Science Foundation of Hunan Province (No. 2022JJ40846).

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Authors and Affiliations

  1. Department of General Practice, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Yuqin Zhang, Wen Zhong & Xia Xu

  2. Department of Orthopedics and Traumatology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China

    Hanxing He

  3. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China

    Xin Fu

  4. Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Ganzhi Liu, Huiying Wang & Bo Chen

  5. Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China

    Bo Chen

  6. Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Biomedical Engineering, Tianjin, China

    Lin Mei

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  1. Yuqin Zhang
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YQ Zhang, B Chen, X Xu, and L Mei designed and drafted the manuscript; YQ Zhang organized the manuscript; B Chen, GZ Liu, HY Wang and Wen Zhong edited the figures; HX He, X Fu, B Chen and X Xia revised the article; all the authors have read and approved the final manuscript.

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Zhang, Y., He, H., Fu, X. et al. Glioblastoma-associated macrophages in glioblastoma: from their function and mechanism to therapeutic advances. Cancer Gene Ther 32, 595–607 (2025). https://doi.org/10.1038/s41417-025-00905-9

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