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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4319-4330. Prepublished online as a Blood First Edition Paper on September 11, 2007; DOI 10.1182/blood-2007-02-072587. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-02-072587v1 110/13/4319    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Duluc, D. Articles by Jeannin, P. Search for Related Content PubMed PubMed Citation Articles by Duluc, D. Articles by Jeannin, P. Related Collections Immunobiology Neoplasia Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Tumor-associated leukemia inhibitory factor and IL-6 skew monocyte differentiation into tumor-associated macrophage-like cells Dorothée Duluc1,2, Yves Delneste1,2, Fang Tan1,2, Marie-Pierre Moles1,4, Linda Grimaud2,5, Julien Lenoir3, Laurence Preisser2,5, Ignacio Anegon6,7, Laurent Catala8, Norbert Ifrah3,4, Philippe Descamps8, Erick Gamelin2,5,9, Hugues Gascan2,5, Mohamed Hebbar10, and Pascale Jeannin1,2,11 1 Inserm, U564, Equipe Avenir, Angers; 2 Université d'Angers, Unité Mixte de Recherche–Santé (UMR-S) 564, Angers; 3 Université d'Angers, Unité Propre de Recherche de l'Enseignement Supérieur (UPRES) EA3863, Angers; 4 Centre Hospitalier Universitaire (CHU) d'Angers, Département des maladies du sang, Angers; 5 Inserm, U564, Angers; 6 Inserm UMR 643, Nantes; 7 Université de Nantes, Institut de Transplantation et de Recherche en Transplantation, Federation of Clinical Immunology Societies (FOCIS), Nantes; 8 CHU d'Angers, Département de Gynécologie, Angers; 9 Centre de lutte contre le Cancer Paul Papin, Angers; 10 CHU de Lille, Département d'Oncologie, Lille; and 11 CHU d'Angers, Laboratoire d'Immunologie et d'Allergologie, Angers, France 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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