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

Author:

Jeannin Pascale,Duluc Dorothée123,Delneste Yves124

Affiliation:

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

2. Université d’Angers, UMR_S 892, Angers, France

3. Baylor Institute for Immunology Research, Dallas, TX, USA

4. CHU d’Angers, Laboratoire d’Immunologie et d’Allergologie, Angers, France

Abstract

Tumor-associated macrophages (TAMs), the most abundant immunosuppressive myeloid cells in the tumor microenvironment, exhibit an IL-10highIL-12low 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.

Publisher

Future Medicine Ltd

Subject

Oncology,Immunology,Immunology and Allergy

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