Oncology, BioDuro LLC, San Diego, CA, United States.
Moores Cancer Center, University of California San Diego, La Jolla, CA, United States.
Front Immunol. 2021 Feb 12;11:626812. doi: 10.3389/fimmu.2020.626812. eCollection 2020.
Cells of the innate immune system are a major component of the tumor microenvironment. They play complex and multifaceted roles in the regulation of cancer initiation, growth, metastasis and responses to therapeutics. Innate immune cells like neutrophils and macrophages are recruited to cancerous tissues by chemotactic molecules released by cancer cells and cancer-associated stromal cells. Once they reach the tumor, they can be instructed by a network of proteins, nucleic acids and metabolites to exert protumoral or antitumoral functions. Altered iron metabolism is a feature of cancer. Epidemiological studies suggest that increased presence of iron and/or iron binding proteins is associated with increased risks of cancer development. It has been shown that iron metabolism is involved in shaping the immune landscapes in inflammatory/infectious diseases and cancer-associated inflammation. In this article, we will dissect the contribution of macrophages and neutrophils to dysregulated iron metabolism in malignant cells and its impact on cancer growth and metastasis. The mechanisms involved in regulating the actions of macrophages and neutrophils will also be discussed. Moreover, we will examine the effects of iron metabolism on the phenotypes of innate immune cells. Both iron chelating and overloading agents are being explored in cancer treatment. This review highlights alternative strategies for management of iron content in cancer cells by targeting the iron donation and modulation properties of macrophages and neutrophils in the tumor microenvironment.
先天免疫系统细胞是肿瘤微环境的主要组成部分。它们在癌症的发生、生长、转移以及对治疗的反应的调控中发挥着复杂而多方面的作用。趋化因子分子由癌细胞和癌相关基质细胞释放,可招募先天免疫细胞(如中性粒细胞和巨噬细胞)到癌组织中。一旦到达肿瘤部位,它们可以被一系列蛋白质、核酸和代谢物所指令,发挥促进肿瘤或抗肿瘤的功能。改变的铁代谢是癌症的一个特征。流行病学研究表明,铁和/或铁结合蛋白的增加与癌症发展风险的增加有关。已经表明,铁代谢参与塑造炎症/感染性疾病和癌症相关炎症中的免疫景观。在本文中,我们将剖析巨噬细胞和中性粒细胞在恶性细胞中失调的铁代谢中的作用,及其对癌症生长和转移的影响。调节巨噬细胞和中性粒细胞作用的机制也将被讨论。此外,我们将研究铁代谢对先天免疫细胞表型的影响。铁螯合剂和铁过载剂都正在被探索用于癌症治疗。本综述强调了通过靶向肿瘤微环境中巨噬细胞和中性粒细胞的铁供体和调节特性来管理癌细胞中铁含量的替代策略。