Therapeutic potential of targeting macrophages and microglia in glioblastoma

Abstract

Glioblastoma (GBM) is a highly aggressive and lethal form of brain tumor in human adults that resists standard of care (SOC) and immunotherapy. Tumor-associated macrophages and microglia (TAMs) represent the most abundant cell population within the GBM tumor microenvironment (TME), comprising up to 50% of the whole tumor mass. TAMs play a pivotal role in promoting tumor progression, driving immunosuppression and inducing therapy resistance. Recent advances have revealed TAM heterogeneity - including their cellular identity (e.g., bone marrow-derived macrophages versus microglia) and the presence of distinct activation/function states and subpopulations within each subtype - in GBM tumors. Targeting the context-dependent TAM infiltration, reprogramming, new subpopulations, survival, phagocytosis, and their interactions with GBM cells in the TME has emerged as a promising therapeutic strategy. Herein we review recent advances in pharmacological targeting of the TAM biology and highlight how these strategies may enhance the effectiveness of SOC and immunotherapies in GBM.

Keywords: glioblastoma; immunotherapy; tumor microenvironment (TME); tumor-associated macrophages and microglia (TAMs).