title: Tumor-associated leukemia inhibitory factor and IL-6 skew monocyte differentiation into tumor-associated macrophage-like cells.
abstract: Tumor-associated macrophages (TAMs), the most abundant immunosuppressive cells in the tumor microenvironment, originate from blood monocytes and exhibit an IL-10(high)IL-12(low) M2 profile. The factors involved in TAM generation remain unidentified. We identify here leukemia inhibitory factor (LIF) and IL-6 as tumor microenvironmental factors that can promote TAM generation. Ovarian cancer ascites switched monocyte differentiation into TAM-like cells that exhibit most ovarian TAM functional and phenotypic characteristics. Ovarian cancer ascites contained high concentrations of LIF and IL-6. Recombinant LIF and IL-6 skew monocyte differentiation into TAM-like cells by enabling monocytes to consume monocyte-colony-stimulating factor (M-CSF). Depletion of LIF, IL-6, and M-CSF in ovarian cancer ascites suppressed TAM-like cell induction. We extended these observations to different tumor-cell line supernatants. In addition to revealing a new tumor-escape mechanism associated with TAM generation via LIF and IL-6, these findings offer novel therapeutic perspectives to subvert TAM-induced immunosuppression and hence improve T-cell-based antitumor immunotherapy efficacy.
authors.affiliation: Inserm, U564, Equipe Avenir, Angers, France.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Duluc
authors.forename: Yves
authors.initials: Y
authors.lastname: Delneste
authors.forename: Fang
authors.initials: F
authors.lastname: Tan
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Moles
authors.forename: Linda
authors.initials: L
authors.lastname: Grimaud
authors.forename: Julien
authors.initials: J
authors.lastname: Lenoir
authors.forename: Laurence
authors.initials: L
authors.lastname: Preisser
authors.forename: Ignacio
authors.initials: I
authors.lastname: Anegon
authors.forename: Laurent
authors.initials: L
authors.lastname: Catala
authors.forename: Norbert
authors.initials: N
authors.lastname: Ifrah
authors.forename: Philippe
authors.initials: P
authors.lastname: Descamps
authors.forename: Erick
authors.initials: E
authors.lastname: Gamelin
authors.forename: Hugues
authors.initials: H
authors.lastname: Gascan
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hebbar
authors.forename: Pascale
authors.initials: P
authors.lastname: Jeannin
mesh_terms: D001201:Ascites; D002454:Cell Differentiation; D003115:Colony-Stimulating Factors; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D053605:Leukemia Inhibitory Factor / Q000502:physiology*; D008264:Macrophages / Q000166:cytology*; D009000:Monocytes / Q000166:cytology*; D010051:Ovarian Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured; D019139:Tumor Escape
chemical_list: D003115:Colony-Stimulating Factors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor