Macrophages and microglia in glioblastoma: heterogeneity, plasticity, and therapy

Glioblastoma (GBM) is the most aggressive tumor in the central nervous system and contains a highly immunosuppressive tumor microenvironment (TME). Tumor-associated macrophages and microglia (TAMs) are a dominant population of immune cells in the GBM TME that contribute to most GBM hallmarks, including immunosuppression. The understanding of TAMs in GBM has been limited by the lack of powerful tools to characterize them. However, recent progress on single cell technologies offers an opportunity to precisely characterize TAMs at the single-cell level and identify new TAM subpopulations with specific tumor-modulatory functions in GBM. In this Review, we discuss TAM heterogeneity and plasticity in the TME and summarize current TAM-targeted therapeutic potential in GBM. We anticipate that the use of single-cell technologies followed by functional studies will accelerate the development of novel and effective TAM targeted therapeutics for GBM patients.

Automated summary

Glioblastoma (GBM) is the most aggressive tumor in the central nervous system and has a highly immunosuppressive tumor microenvironment (TME). Tumor-associated macrophages and microglia (TAMs) are dominant immune cells in the GBM TME and contribute to immunosuppression. Recent progress in single cell technologies allows for precise characterization of TAMs and identification of new TAM subpopulations with specific tumor-modulating functions in GBM. This review discusses TAM heterogeneity and plasticity in the TME and summarizes current potential therapeutic approaches targeting TAMs in GBM. The use of single cell technologies and functional studies is expected to accelerate the development of novel and effective TAM targeted therapeutics for GBM patients.