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Blood, 25 June 2009, Vol. 113, No. 26, pp. 6658-6668. Prepublished online as a Blood First Edition Paper on March 12, 2009; DOI 10.1182/blood-2008-06-161075. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-06-161075v1 113/26/6658    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 Google Scholar Articles by Zarei, S. Articles by Mach, N. PubMed PubMed Citation Articles by Zarei, S. Articles by Mach, N. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Role of GM-CSF signaling in cell-based tumor immunization Shohreh Zarei1, Frank Schwenter1,2, Patricia Luy1, Michel Aurrand-Lions3, Philippe Morel2, Manfred Kopf4, Glenn Dranoff5, and Nicolas Mach1 1 Oncology Division, Department of Internal Medicine, and 2 Visceral and Transplantation Unit, Department of Surgery, Geneva University Hospital and Geneva Medical School, Geneva, Switzerland; 3 Paoli-Calmettes Institute, Inserm, Cancer Research Center, Marseille, France; 4 Department of Environmental Science, Swiss Federal Institute of Technology, Zurich, Switzerland; and 5 Department of Adult Oncology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, MA Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent adjuvant in cancer vaccination; however, the specific role of endogenous GM-CSF remains unknown. We performed cell-based vaccination in 2 tumor models. First, we vaccinated C57BL/6 mice lacking either GM-CSF, IL-5, or beta-common chain (βc), a receptor subunit essential for GM-CSF and IL-5 signaling, with melanoma cells engineered to produce GM-CSF. Tumor vaccination was effective in both GM-CSF–/– and IL-5–/– mice, showing that protective immunization is independent of both endogenous cytokines. However, all βc–/– animals developed tumor. Loss of tumor immunity in βc–/– mice does not reflect global impairment in cell-mediated immunity, as contact hypersensitivity reaction to haptens is unaltered. The importance of tumor cell–derived GM-CSF was highlighted by recruitment of dendritic cells at the vaccination site in wild-type, GM-CSF–/–, and IL-5–/– but not in βc–/– mice. In the second model, vaccination with unmodified RENCA cells showed similar results with efficient immunization in BALB/c wild-type and GM-CSF–/–, whereas all βc–/– animals died. Altogether, our results strongly suggest that although endogenous GM-CSF and IL-5 are not required to induce tumor immunity, signaling through βc receptor is critically needed for efficient cancer vaccination in both genetically modified GM-CSF–secreting tumor cells and a spontaneously immunogenic models. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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