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These tumor\u2010associated macrophages (TAM) exhibit an M2\u2010like profile, with deficient production of NO and ROS, characteristics of pro\u2010inflammatory M1 cytotoxic macrophages. Lipoxins (LX) and 15\u2010epi\u2010lipoxins are lipid mediators which can induce certain features of M2 macrophages in mononuclear cells, but their effects on TAM remain to be elucidated. This study tested the hypothesis that ATL\u20101, a synthetic analogue of 15\u2010epi\u2010lipoxin A<jats:sub>4<\/jats:sub>, could modulate TAM activity profile. We show that human macrophages (M\u03a6) differentiated into TAM\u2010like cells after incubation with conditioned medium from MV3, a human melanoma lineage cell. Contrasting with the effects observed in other M2 subsets and M1 profile macrophages, ATL\u20101 selectively decreased M2 surface markers in TAM, suggesting unique behavior of this particular M2 subset. Importantly, these results were replicated by the natural lipoxins LXA<jats:sub>4<\/jats:sub> and the aspirin induced 15\u2010epi\u2010LXA<jats:sub>4<\/jats:sub> (ATL). In parallel, ATL\u20101 stimulated TAM to produce NO by increasing the iNOS\/arginase ratio and activated NADPH oxidase, triggering ROS production. These alterations in TAM profile induced by ATL\u20101 led to loss of the anti\u2010apoptotic effects of TAM on melanoma cells and increased their cytotoxic properties. Finally, ATL\u20101 was found to inhibit tumor progression in a murine model <jats:italic>in vivo<\/jats:italic>, which was accompanied by alterations in TAM profile and diminished angiogenesis. Together, the results show an unexpected effect of lipoxin, which induces in TAM a change from an M2\u2010 to an M1\u2010like profile, thereby triggering tumor cell apoptosis and down\u2010modulating the tumor progression.<\/jats:p>","DOI":"10.1002\/ijc.30424","type":"journal-article","created":{"date-parts":[[2016,9,12]],"date-time":"2016-09-12T08:36:53Z","timestamp":1473669413000},"page":"346-357","source":"Crossref","is-referenced-by-count":57,"title":["Lipoxin A<sub>4<\/sub> selectively programs the profile of M2 tumor\u2010associated macrophages which favour control of tumor progression"],"prefix":"10.1002","volume":"140","author":[{"given":"R. L.","family":"Sim\u00f5es","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia Celular e Molecular, IBRAG, Universidade do Estado do Rio de Janeiro Rio de Janeiro RJ Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. 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