Emerging strategies for targeting tumor-associated macrophages in glioblastoma: A focus on chemotaxis blockade

Abstract

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, with poor prognosis for affected patients. A key player in the GBM tumor microenvironment is the tumor-associated macrophage (TAM), which promotes tumor progression, immune evasion, and therapeutic resistance. The recruitment of TAMs to the tumor site is driven by specific chemotactic signals, including CSF-1/CSF-1R, CXCR4/CXCL12, and HGF/MET pathways. This review explores the current understanding of these chemotaxis mechanisms and their role in GBM progression. It highlights the potential therapeutic benefits of targeting TAM chemotaxis pathways to disrupt TAM infiltration, reduce immunosuppression, and enhance the efficacy of conventional treatments. Additionally, we discuss the preclinical and clinical evidence surrounding key inhibitors, such as PLX3397, AMD3100, and Crizotinib, which have shown promise in reprogramming TAMs and improving treatment outcomes in GBM. While these strategies offer hope for overcoming some of the challenges of GBM therapy, the review also addresses the limitations and obstacles in clinical translation, emphasizing the need for further research and the development of combination therapies to achieve sustained therapeutic benefit.