Mitochondrial DNA on Tumor-Associated Macrophages Polarization and Immunity

SIMPLE SUMMARY: As the most abundant cell in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) drive tumor progress by inducing angiogenesis, fibrosis, invasion, metastasis, and immunosuppression, which makes these cells an important target for tumor treatment. Recently, the role of free mitochondrial DNA (mtDNA) has attracted increased attention in the regulation of immune cells in the TME. In this review, we first summarize the functional characteristics of macrophages in tumor progression. The release and regulation mechanisms of tumor cell-derived mtDNA in TME are also introduced. Then, the biological effects of endogenous and exogenous mtDNA on macrophages are discussed. Finally, we propose that the effect of mtDNA on macrophages is worthy of attention in the process of tumor treatment, especially in immunotherapy. Our review provides a systematic summary of the effects of mtDNA on the survival, function, and phenotypes of TAMs in the TME. ABSTRACT: As the richest immune cells in most tumor microenvironments (TMEs), tumor-associated macrophages (TAMs) play an important role in tumor development and treatment sensitivity. The phenotypes and functions of TAMs vary according to their sources and tumor progression. Different TAM phenotypes display distinct behaviors in terms of tumor immunity and are regulated by intracellular and exogenous molecules. Additionally, dysfunctional and oxidatively stressed mitochondrial-derived mitochondrial DNA (mtDNA) plays an important role in remodeling the phenotypes and functions of TAMs. This article reviews the interactions between mtDNA and TAMs in the TME and further discusses the influence of their performance on tumor genesis and development.