title: IL-6 and leukemia-inhibitory factor are involved in the generation of tumor-associated macrophage: regulation by IFN-γ.
abstract: Tumor-associated macrophages (TAMs), the most abundant immunosuppressive myeloid cells in the tumor microenvironment, exhibit an IL-10(high)IL-12(low) profile called M2, opposite to the immunostimulatory M1. We reported that ovarian cancer ascites switched monocyte differentiation into TAM-like cells that exhibit most phenotypic and functional characteristics of TAMs, suggesting that soluble mediators are involved in the differentiation of monocytes into TAM-like cells. We observed that leukemia-inhibitory factor and IL-6, present at high concentrations in ovarian cancer ascites, skew monocyte differentiation into TAM-like cells by increasing macrophage colony-stimulating factor consumption. Moreover, we observed that IFN-γ switches established TAMs into immunostimulatory M1 cells and skews monocyte differentiation from TAM-like cells to M1s. In addition to revealing a new tumor-escape mechanism associated with TAM generation via leukemia-inhibitory factor and IL-6, these findings offer novel therapeutic perspectives to subvert TAM-induced immunosuppression and to improve antitumor immunotherapy efficacy.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 892, Centre de Recherche en Cancérologie Nantes-Angers, Angers, France. pascale.jeannin@univ-angers.fr
authors.forename: Pascale
authors.initials: P
authors.lastname: Jeannin
authors.forename: Dorothée
authors.initials: D
authors.lastname: Duluc
authors.forename: Yves
authors.initials: Y
authors.lastname: Delneste
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009000:Monocytes / Q000473:pathology; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D019139:Tumor Escape; D059016:Tumor Microenvironment
chemical_list: D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D007371:Interferon-gamma