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.
Highlights
Brain cancer is the leading cause of cancer-related deaths in patients younger than 35 (Wen and Kesari, 2008)
GBM tumor microenvironment is predominated by a heterogenous population of myeloid cells composed of brain-resident microglia and bone-marrow-derived macrophages, which are collectively referred to as tumor-associated macrophages and microglia (TAMs)
For blood-derived macrophages, three clusters were identified: one characterized by an inflammatory monocyte signature (Ly6c2, Ccr2, Tgfbi), one with intermediate state of mixed monocytes and macrophage signature (Ly6c2, Tgfbi), and one with differentiated macrophage signature (Ly6c2, Ifitm2, Ifitm3, S100a6) (Ochocka et al, 2019). These findings demonstrate the dynamic plasticity of both microglia and macrophages in the tumor microenvironment
Summary
Brain cancer is the leading cause of cancer-related deaths in patients younger than 35 (Wen and Kesari, 2008). Glioblastoma (GBM) accounts for 70% of malignant primary brain tumors, taking more than 13,000 lives in the United States each year (Wen and Kesari, 2008). GBM tumor microenvironment is predominated by a heterogenous population of myeloid cells composed of brain-resident microglia and bone-marrow-derived macrophages, which are collectively referred to as tumor-associated macrophages and microglia (TAMs). TAMs represent about 40% of tumor mass in GBM (Kennedy et al, 2013). Mitochondrial dysfunction is a hallmark of GBM. Current studies mostly focus on the impact of mitochondrial dysfunction on intrinsic tumor function. How tumor mitochondrial dysfunction influences the function of non-tumor cells such as TAMs is not well-studied. Mitochondrial Dysfunction and Cancer Immunity glioma and provide our perspective on how GBM mitochondrial dysfunction can regulate immune response in the tumor microenvironment
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