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10.3390/cells15060508
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Article

Molecular Determinants of Macrophage Polarization in Glioblastoma and Implications for Tumor Progression

by
Xiao-Xiao Luo
1,†,
Min Fu
1,†,
Ben Zhao
1,
Feng Yang
1,
Yi-Zhou Liu
1,
Xiao-Hong Peng
1,
Shi-Yong Li
2,
Gao-Feng Zhan
2,
Ying-Jia Hu
3,
Guang-Yuan Hu
1,
Heng-Hui Cheng
4,* and
Qian-Xia Li
1,*
1
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
2
Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
3
Department of Public Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA
4
Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cells 2026, 15(6), 508; https://doi.org/10.3390/cells15060508
Submission received: 15 January 2026 / Revised: 6 February 2026 / Accepted: 5 March 2026 / Published: 13 March 2026
(This article belongs to the Special Issue Role of Gene Regulation in Neurological Disorders)
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Abstract

Glioblastoma (GBM) is a highly aggressive brain tumor with a complex tumor microenvironment (TME) that includes immune cell infiltration, notably macrophages. The role of macrophages in GBM progression is influenced by their polarization state, which can be either pro-inflammatory (M1) or immunosuppressive (M2). This study investigates the macrophage polarization in GBM, identifying key macrophage-related genes and their impact on tumor progression. Analysis of TCGA-GBM data revealed that macrophage infiltration correlates with poor prognosis, with 41 risk-associated genes identified. DSP dataset analysis highlighted 378 differentially expressed genes between CD68+ macrophages and GFAP+ controls, including immune-related genes like SPP1, CD74, and C3. Cross-validation with single-cell RNA-seq confirmed the expression of 9 key genes, with 7 genes being macrophage-specific. In vitro experiments using conditioned media from GBM cell lines demonstrated that GBM cells promote macrophage polarization towards an M2-like phenotype. Overexpression of CD74, CLEC7A, and IFI30 in macrophages further enhanced M2 polarization, which was associated with increased tumor-promoting functions, including enhanced invasion and reduced apoptosis in GBM cells. Together, these findings highlight the role of M2 macrophage polarization in promoting GBM progression and suggest that targeting macrophage polarization pathways may offer therapeutic potential.
Keywords: glioblastoma; macrophage; polarization glioblastoma; macrophage; polarization
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MDPI and ACS Style

Luo, X.-X.; Fu, M.; Zhao, B.; Yang, F.; Liu, Y.-Z.; Peng, X.-H.; Li, S.-Y.; Zhan, G.-F.; Hu, Y.-J.; Hu, G.-Y.; et al. Molecular Determinants of Macrophage Polarization in Glioblastoma and Implications for Tumor Progression. Cells 2026, 15, 508. https://doi.org/10.3390/cells15060508

AMA Style

Luo X-X, Fu M, Zhao B, Yang F, Liu Y-Z, Peng X-H, Li S-Y, Zhan G-F, Hu Y-J, Hu G-Y, et al. Molecular Determinants of Macrophage Polarization in Glioblastoma and Implications for Tumor Progression. Cells. 2026; 15(6):508. https://doi.org/10.3390/cells15060508

Chicago/Turabian Style

Luo, Xiao-Xiao, Min Fu, Ben Zhao, Feng Yang, Yi-Zhou Liu, Xiao-Hong Peng, Shi-Yong Li, Gao-Feng Zhan, Ying-Jia Hu, Guang-Yuan Hu, and et al. 2026. "Molecular Determinants of Macrophage Polarization in Glioblastoma and Implications for Tumor Progression" Cells 15, no. 6: 508. https://doi.org/10.3390/cells15060508

APA Style

Luo, X.-X., Fu, M., Zhao, B., Yang, F., Liu, Y.-Z., Peng, X.-H., Li, S.-Y., Zhan, G.-F., Hu, Y.-J., Hu, G.-Y., Cheng, H.-H., & Li, Q.-X. (2026). Molecular Determinants of Macrophage Polarization in Glioblastoma and Implications for Tumor Progression. Cells, 15(6), 508. https://doi.org/10.3390/cells15060508

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