Tumor-Associated Macrophages as a Paradigm of Macrophage Plasticity, Diversity, and Polarization: Lessons and Open Questions
Tumor-Associated Macrophages as a Paradigm of Macrophage Plasticity, Diversity, and Polarization: Lessons and Open Questions
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DOI：
10.1161/atvbaha.113.300168
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发表时间：
2013-07-01
影响因子：
8.7
通讯作者：
Locati, Massimo
中科院分区：
文献类型：
--
作者：
Mantovani, Alberto;Locati, Massimo
巨噬细胞存在于所有身体区室，包括癌组织，并且它们的功能受到来自稳态和病理条件下的微环境的信号的深刻影响。肿瘤相关巨噬细胞是癌症相关炎症的主要细胞组分，并且已经充当单核吞噬细胞的可塑性和功能极化的范例。肿瘤相关巨噬细胞可以根据激活状态发挥癌症的双重影响，经典激活（M1）和交替激活（M2）细胞通常分别发挥抗肿瘤和促肿瘤功能。这些是多样性宇宙中极化状态连续体的极端。肿瘤相关巨噬细胞几乎影响肿瘤组织的所有方面，包括干细胞、代谢、血管生成、侵袭和转移。在确定信号分子、转录因子、表观遗传变化和巨噬细胞极化的microRNA库方面已经取得了进展。临床前和早期临床数据表明，巨噬细胞可作为开发癌症和慢性非消退性炎症性疾病的创新诊断和治疗策略的工具。
Macrophages are present in all body compartments, including cancerous tissues, and their functions are profoundly affected by signals from the microenvironment under homeostatic and pathological conditions. Tumor-associated macrophages are a major cellular component of cancer-related inflammation and have served as a paradigm for the plasticity and functional polarization of mononuclear phagocytes. Tumor-associated macrophages can exert dual influence of cancer depending on the activation state, with classically activated (M1) and alternatively activated (M2) cells generally exerting antitumoral and protumoral functions, respectively. These are extremes in a continuum of polarization states in a universe of diversity. Tumor-associated macrophages affect virtually all aspects of tumor tissues, including stem cells, metabolism, angiogenesis, invasion, and metastasis. Progress has been made in defining signaling molecules, transcription factors, epigenetic changes, and repertoire of microRNAs underlying macrophage polarization. Preclinical and early clinical data suggest that macrophages may serve as tools for the development of innovative diagnostic and therapeutic strategies in cancer and chronic nonresolving inflammatory diseases.