Abstract
Glioblastoma is the most aggressive and lethal cancer of the central nervous system, presenting substantial treatment challenges. The current standard treatment, which includes surgical resection followed by temozolomide and radiation, offers limited success. While immunotherapies, such as immune checkpoint inhibitors, have proven effective in other cancers, they have not demonstrated significant efficacy in GBM. Emerging research highlights the pivotal role of tumor-associated macrophages (TAMs) in supporting tumor growth, fostering treatment resistance, and shaping an immunosuppressive microenvironment. Preclinical studies show promising results for therapies targeting TAMs, suggesting potential in overcoming these barriers. TAMs consist of brain-resident microglia and bone marrow-derived macrophages, both exhibiting diverse phenotypes and functions within the tumor microenvironment. This review delves into the origin, heterogeneity, and functional roles of TAMs in GBM, underscoring their dual roles in tumor promotion and suppression. It also summarizes recent progress in TAM-targeted therapies, which may, in combination with other treatments like immunotherapy, pave the way for more effective and personalized strategies against this aggressive malignancy.