肿瘤相关巨噬细胞的线粒体调控

Mitochondrial Regulation of Tumor-associated Macrophages

肿瘤免疫微环境是肿瘤发生发展的重要微生态,肿瘤相关巨噬细胞是肿瘤免疫微环境中最丰富的免疫细胞,具有高度可塑性和异质性。受各种环境因素的调控,肿瘤相关巨噬细胞可分化为肿瘤促进或肿瘤抑制的不同亚群。这些环境因素复杂多变,但最终都是通过影响细胞内部组分、结构和功能的时间以及空间异质性来调控肿瘤相关巨噬细胞。线粒体是重要的细胞器,负责能量产生、物质代谢,也是多种信号传导的中枢。越来越多的研究发现,线粒体可以通过形态改变、代谢重编程、中间代谢产物或线粒体遗传物质等多种机制调控细胞功能。本文综述了线粒体调控巨噬细胞极化、重塑肿瘤免疫微环境的机制,并针对巨噬细胞线粒体相关肿瘤免疫治疗的现状进行了讨论和展望。

Tumor immune microenvironment is an important microecology for tumor development,where tumor-associated macrophages are the most abundant immune cells in the tumor immune microenvironment,with high plasticity and heterogeneity.Under the regulation of various environmental factors,tumor-associated macrophages can differentiate into different subgroups.Though complex and variable,all these environmental factors ultimately regulate tumor-associated macrophages by influencing the temporal and spatial heterogeneity of these cells’internal components,structure,and functions.Mitochondrion are important organelles,responsible for energy production,metabolism,and centers of multiple signal transduction.More and more studies have found that mitochondria can regulate cell functions through various mechanisms such as morphological change,metabolic reprogramming,intermediate metabolites or mitochondrial genetic material.Mitochondrial disorders are involved in many diseases and pathological processes.Here,we review the mechanisms by which mitochondria regulate the polarization of macrophages and thus reshape the tumor immune microenvironment.Further,we discuss and prospect the current status of macrophage mitochondria-related tumor immunotherapy.