Myeloid Cells in Glioblastoma Microenvironment

Abstract

Glioblastoma (GBM) is the most aggressive, malignant primary brain tumor in adults. GBM is notoriously resistant to immunotherapy mainly due to its unique immune microenvironment. High dimensional data analysis reveals the extensive heterogeneity of immune components making up the GBM microenvironment. Myeloid cells are the most predominant contributors to the GBM microenvironment; these cells are critical regulators of immune and therapeutic responses to GBM. Here, we will review the most recent advances on the characteristics and functions of different populations of myeloid cells in GBM, including bone marrow-derived macrophages, microglia, myeloid-derived suppressor cells, dendritic cells, and neutrophils. Epigenetic, metabolic, and phenotypic peculiarities of microglia and bone marrow-derived macrophages will also be assessed. The final goal of this review will be to provide new insights into novel therapeutic approaches for specific targeting of myeloid cells to improve the efficacy of current treatments in GBM patients.

Keywords: brain cancers; dendritic cells; glioblastoma; glioma; microglia; myeloid cells; myeloid-derived suppressor cells; neutrophils; tumor-associated macrophages.

Figure 1

Myeloid cell compartment in the GBM tumor microenvironment. Surface molecules for the identification of myeloid cells are shown along with main characteristics and functions.

Figure 2

Targeting myeloid cells in GBM. Different approaches aimed to deplete and to inhibit functions and recruitment of MDSCs and TAMs are used to reduce the immunosuppression. DC vaccines and approaches aimed to increase accumulation, activation, and functions of DCs are used to stimulate effector functions.