The Role of Myeloid Cells in GBM Immunosuppression

Abstract

Gliomas are intrinsic brain tumors that originate from glial cells. Glioblastoma (GBM) is the most aggressive glioma type and resistant to immunotherapy, mainly due to its unique immune environment. Dimensional data analysis reveals that the intra-tumoral heterogeneity of immune cell populations in the glioma microenvironment is largely made up of cells of myeloid lineage. Conventional therapies of combined surgery, chemotherapy and radiotherapy have achieved limited improvements in the prognosis of glioma patients, as myeloid cells are prominent mediators of immune and therapeutic responses—like immunotherapy resistance—in glioma. Myeloid cells are frequently seen in the tumor microenvironment (TME), and they are polarized to promote tumorigenesis and immunosuppression. Reprogramming myeloid cells has emerged as revolutionary, new types of immunotherapies for glioma treatment. Here we detail the current advances in classifying epigenetic, metabolic, and phenotypic characteristics and functions of different populations of myeloid cells in glioma TME, including myeloid-derived suppressor cells (MDSCs), glioma-associated microglia/macrophages (GAMs), glioma-associated neutrophils (GANs), and glioma-associated dendritic cells (GADCs), as well as the mechanisms underlying promotion of tumorigenesis. 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 glioma patients.