Laoui Damya, Movahedi Kiavash, Van Overmeire Eva, Van den Bossche Jan, Schouppe Elio, Mommer Camille, Nikolaou Alexandros, Morias Yannick, De Baetselier Patrick, Van Ginderachter Jo A
Lab of Cellular and Molecular Immunology and Lab of Cellular and Molecular Immunology, Department of Molecular and Cellular Interactions, Vrije Universiteit Brussel, Pleinlaan 2, Brussels, Belgium.
Int J Dev Biol. 2011;55(7-9):861-7. doi: 10.1387/ijdb.113371dl.
Macrophages display remarkable plasticity, allowing these cells to adapt to changing microenvironments and perform functions as diverse as tissue development and homeostasis, inflammation, pathogen clearance and wound healing. Macrophage activation can be triggered by Th1 cytokines and pathogen-associated or endogenous danger signals, leading to the formation of classically activated or M1 macrophages. On the other hand, anti-inflammatory mediators, including IL-4, IL-10, TGF-β and M-CSF, induce diverse anti-inflammatory types of macrophages, known under the generic term M2. In human breast carcinomas, tumor-associated macrophage (TAM) density correlates with poor prognosis. In mouse models of breast cancer, eliminating macrophages from the tumor site, either via genetic or therapeutic means, results in retarded tumor progression. Over the years, multiple signals from the mammary tumor microenvironment have been reported to influence the TAM phenotype and TAM have been propagated as anti-inflammatory M2-like cells. Recent developments point to the existence of at least two distinct TAM subpopulations in mammary tumors, based on a differential expression of markers such as CD206 or MHC II and different in vivo behaviour: perivascular, migratory TAM which are less M2-like, and sessile TAM found at tumor-stroma borders and/or hypoxic regions that resemble more M2-like or "trophic" macrophages. Hence, a further refinement of the molecular and functional heterogeneity of TAM is an avenue for further research, with a potential impact on the usefulness of these cells as therapeutic targets.
巨噬细胞表现出显著的可塑性，使这些细胞能够适应不断变化的微环境，并执行诸如组织发育与稳态、炎症、病原体清除和伤口愈合等多种功能。巨噬细胞的激活可由Th1细胞因子以及病原体相关或内源性危险信号触发，导致经典激活的或M1巨噬细胞的形成。另一方面，包括IL-4、IL-10、TGF-β和M-CSF在内的抗炎介质可诱导多种抗炎类型的巨噬细胞，统称为M2。在人类乳腺癌中，肿瘤相关巨噬细胞（TAM）密度与预后不良相关。在乳腺癌小鼠模型中，通过基因或治疗手段从肿瘤部位清除巨噬细胞会导致肿瘤进展迟缓。多年来，有报道称来自乳腺肿瘤微环境的多种信号会影响TAM表型，并且TAM已被认为是抗炎性M2样细胞。最近的研究进展表明，基于CD206或MHC II等标志物的差异表达以及不同的体内行为，乳腺肿瘤中至少存在两种不同的TAM亚群：血管周围的、迁移性的TAM，其M2样特征较少；以及位于肿瘤-基质边界和/或缺氧区域的固着性TAM，则更类似于M2样或“营养性”巨噬细胞。因此，进一步细化TAM的分子和功能异质性是一个有待深入研究的方向，可能会影响这些细胞作为治疗靶点的实用性。
