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

Blood. 2007 Dec 15;110(13):4319-30. doi: 10.1182/blood-2007-02-072587. Epub 2007 Sep 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ascites
  • Cell Differentiation*
  • Colony-Stimulating Factors
  • Female
  • Humans
  • Interleukin-6 / physiology*
  • Leukemia Inhibitory Factor / physiology*
  • Macrophages / cytology*
  • Monocytes / cytology*
  • Ovarian Neoplasms / pathology*
  • Tumor Cells, Cultured
  • Tumor Escape


  • Colony-Stimulating Factors
  • Interleukin-6
  • LIF protein, human
  • Leukemia Inhibitory Factor