Glioma-associated microglia/macrophages (GAMs) in glioblastoma: Immune function in the tumor microenvironment and implications for immunotherapy

Abstract

Glioma is a mixed solid tumor composed of neoplastic and non-neoplastic components. Glioma-associated macrophages and microglia (GAMs) are crucial elements of the glioma tumor microenvironment (TME), regulating tumor growth, invasion, and recurrence. GAMs are also profoundly influenced by glioma cells. Recent studies have revealed the intricate relationship between TME and GAMs. In this updated review, we provide an overview of the interaction between glioma TME and GAMs based on previous studies. We also summarize a series of immunotherapies targeting GAMs, including clinical trials and preclinical studies. Specifically, we discuss the origin of microglia in the central nervous system and the recruitment of GAMs in the glioma background. We also cover the mechanisms through which GAMs regulate various processes associated with glioma development, such as invasiveness, angiogenesis, immunosuppression, recurrence, etc. Overall, GAMs play a significant role in the tumor biology of glioma, and a better understanding of the interaction between GAMs and glioma could catalyze the development of new and effective immunotherapies for this deadly malignancy.

Keywords: glioblastoma; glioma; glioma-associated macrophage and microglia; immunotherapy; tumor microenvironment.