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Blood, 1 July 2006, Vol. 108, No. 1, pp. 228-237. Prepublished online as a Blood First Edition Paper on March 7, 2006; DOI 10.1182/blood-2005-08-3507. This Article Full Text Full Text (PDF) Supplemental Table and Figure All Versions of this Article: 2005-08-3507v1 108/1/228    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by von Bergwelt-Baildon, M. S. Articles by Schultze, J. L. Search for Related Content PubMed PubMed Citation Articles by von Bergwelt-Baildon, M. S. Articles by Schultze, J. L. Related Collections Signal Transduction Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY CD25 and indoleamine 2,3-dioxygenase are up-regulated by prostaglandin E2 and expressed by tumor-associated dendritic cells in vivo: additional mechanisms of T-cell inhibition Michael S. von Bergwelt-Baildon, Alexey Popov, Tomo Saric, Jens Chemnitz, Sabine Classen, Marc S. Stoffel, Francesca Fiore, Udo Roth, Marc Beyer, Svenja Debey, Claudia Wickenhauser, Franz-Georg Hanisch, and Joachim L. Schultze From the Molecular Tumor Biology and Tumor Immunology, the Clinic I for Internal Medicine, Hematology and Oncology, the Institute of Neurophysiology, the Institute for Biochemistry II, and the Institute for Pathology, University Hospital at the University of Cologne, Germany. Immune tolerance is a central mechanism counteracting tumor-specific immunity and preventing effective anticancer immunotherapy. Induction of tolerance requires a specific environment in which tolerogenic dendritic cells (DCs) play an essential role deviating the immune response away from effective immunity. It was recently shown that maturation of DCs in the presence of PGE2 results in upregulation of indoleamine 2,3-dioxygenase (IDO) providing a potential mechanism for the development of DC-mediated Tcell tolerance. Here, we extend these findings, demonstrating a concomitant induction of IDO and secretion of soluble CD25 after DC maturation in the presence of PGE2. While maturation of DCs induced IDO expression on transcriptional level, only integration of PGE2 signaling led to up-regulation of functional IDO protein as well as significant expression of cell-surface and soluble CD25 protein. As a consequence, T-cell proliferation and cytokine production were significantly inhibited, which was mediated mainly by IDO-induced tryptophan depletion. Of importance, we demonstrate that different carcinoma entities associated with elevated levels of PGE2 coexpress CD25 and IDO in peritumoral dendritic cells, suggesting that PGE2 might influence IDO expression in human DCs in the tumor environment. We therefore suggest PGE2 to be a mediator of early events during induction of immune tolerance in cancer. (Blood. 2006;108:228-237) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Cools, P. Ponsaerts, V. F. I. Van Tendeloo, and Z. N. Berneman Balancing between immunity and tolerance: an interplay between dendritic cells, regulatory T cells, and effector T cells J. Leukoc. Biol., December 1, 2007; 82(6): 1365 - 1374. [Abstract] [Full Text] [PDF] N. Bles, M. Horckmans, A. Lefort, F. Libert, P. Macours, H. El Housni, F. Marteau, J.-M. Boeynaems, and D. Communi Gene Expression Profiling Defines ATP as a Key Regulator of Human Dendritic Cell Functions J. Immunol., September 15, 2007; 179(6): 3550 - 3558. [Abstract] [Full Text] [PDF] D.-Y. Hou, A. J. Muller, M. D. Sharma, J. DuHadaway, T. Banerjee, M. Johnson, A. L. Mellor, G. C. Prendergast, and D. H. Munn Inhibition of Indoleamine 2,3-Dioxygenase in Dendritic Cells by Stereoisomers of 1-Methyl-Tryptophan Correlates with Antitumor Responses Cancer Res., January 15, 2007; 67(2): 792 - 801. [Abstract] [Full Text] [PDF]

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