Tumor-associated leukemia inhibitory factor and IL-6 skew monocyte differentiation into tumor-associated macrophage-like cells

D Duluc, Y Delneste, F Tan, MP Moles… - Blood, The Journal …, 2007 - ashpublications.org
D Duluc, Y Delneste, F Tan, MP Moles, L Grimaud, J Lenoir, L Preisser, I Anegon, L Catala…
Blood, The Journal of the American Society of Hematology, 2007ashpublications.org
Tumor-associated macrophages (TAMs), the most abundant immunosuppressive cells in the
tumor microenvironment, originate from blood monocytes and exhibit an IL-10highIL-12low
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 …
Tumor-associated macrophages (TAMs), the most abundant immunosuppressive cells in the tumor microenvironment, originate from blood monocytes and exhibit an IL-10highIL-12low 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.
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