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

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.