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Immunotherapy. 2011 Apr;3(4 Suppl):23-6. doi: 10.2217/imt.11.30.

IL-6 and leukemia-inhibitory factor are involved in the generation of tumor-associated macrophage: regulation by IFN-γ.

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  • 1Institut National de la Santé et de la Recherche Médicale, Unité 892, Centre de Recherche en Cancérologie Nantes-Angers, Angers, France.


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.

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