Mitochondrial Dysfunction, Macrophage, and Microglia in Brain Cancer

Front Cell Dev Biol. 2021 Jan 15:8:620788. doi: 10.3389/fcell.2020.620788. eCollection 2020.

Abstract

Glioblastoma (GBM) is the most common malignant brain cancer. Increasing evidence suggests that mitochondrial dysfunction plays a key role in GBM progression as mitochondria is essential in regulating cell metabolism, oxidative stress, and cell death. Meanwhile, the immune microenvironment in GBM is predominated by tumor-associated macrophages and microglia (TAM), which is a heterogenous population of myeloid cells that, in general, create an immunosuppressive milieu to support tumor growth. However, subsets of TAMs can be pro-inflammatory and thereby antitumor. Therapeutic strategies targeting TAMs are increasingly explored as novel treatment strategies for GBM. The connection between mitochondrial dysfunction and TAMs phenotype in the tumor microenvironment is unclear. This review aims to provide perspectives and discuss possible molecular mechanisms mediating the interplay between glioma mitochondrial dysfunction and TAMs phenotype in shaping tumor immune microenvironment.

Keywords: brain cancer; inflammatory response; mitochondrial DNA; mitochondrial dysfunction; tumor associated macrophages and microglia.