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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 (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 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 HighWire 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 20, 2007 Accepted August 29, 2007 Tumor-associated leukemia inhibitory factor and IL-6 skew monocyte differentiation into tumor-associated-macrophage-like cells Dorothee Duluc, Yves Delneste, Fang Tan, Marie-Pierre Moles, Linda Grimaud, Julien Lenoir, Laurence Preisser, Ignacio Anegon, Laurent Catala, Norbert Ifrah, Philippe Descamps, Erick Gamelin, Hugues Gascan, Mohamed Hebbar, and Pascale Jeannin* Equipe AVENIR, Inserm U564, Angers, France UMR-S 564, Universite d'Angers, Angers, France UPRES EA3863, Universite d'Angers, Angers, France Universite de Nantes, Institut de Transplantation et de Recherche en Transplantation, FOCIS, Nantes, France Departement de Gynecologie, CHU d'Angers, Angers, France Departement des Maladies du sang, CHU d'Angers, Angers, France Centre de lutte contre le Cancer Paul Papin, Angers, France Inserm U564, Angers, France Departement d'Oncologie, CHU de Lille, Lille, France Laboratoire d'Immunologie et d'Allergologie, CHU d'Angers, Angers, France * Corresponding author; email: pascale.jeannin{at}univ-angers.fr. Tumor-associated macrophages (TAM), 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 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 to TAM generation via LIF and IL-6, these findings offer novel therapeutic perspectives to subvert TAM-induced immunosuppression and hence improve T-cell-based anti-tumor immunotherapy efficacy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Colotta, P. Allavena, A. Sica, C. Garlanda, and A. Mantovani Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability Carcinogenesis, July 1, 2009; 30(7): 1073 - 1081. [Abstract] [Full Text] [PDF]

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