title: Tumor-associated macrophages in breast cancer: distinct subsets, distinct functions.
abstract: 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.
authors.affiliation: 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.
authors.forename: Damya
authors.initials: D
authors.lastname: Laoui
authors.forename: Kiavash
authors.initials: K
authors.lastname: Movahedi
authors.forename: Eva
authors.initials: E
authors.lastname: Van Overmeire
authors.forename: Jan
authors.initials: J
authors.lastname: Van den Bossche
authors.forename: Elio
authors.initials: E
authors.lastname: Schouppe
authors.forename: Camille
authors.initials: C
authors.lastname: Mommer
authors.forename: Alexandros
authors.initials: A
authors.lastname: Nikolaou
authors.forename: Yannick
authors.initials: Y
authors.lastname: Morias
authors.forename: Patrick
authors.initials: P
authors.lastname: De Baetselier
authors.forename: Jo A
authors.initials: JA
authors.lastname: Van Ginderachter
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D002450:Cell Communication; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D008262:Macrophage Activation; D008264:Macrophages / Q000145:classification* / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008954:Models, Biological; D011379:Prognosis
chemical_list: D018836:Inflammation Mediators