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Blood, 15 April 2008, Vol. 111, No. 8, pp. 4233-4244. Prepublished online as a Blood First Edition Paper on February 13, 2008; DOI 10.1182/blood-2007-07-099226. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-07-099226v1 111/8/4233    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 Movahedi, K. Articles by Van Ginderachter, J. A. PubMed PubMed Citation Articles by Movahedi, K. Articles by Van Ginderachter, J. A. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell–suppressive activity Kiavash Movahedi1,2, Martin Guilliams1,2, Jan Van den Bossche1,2, Rafael Van den Bergh1,2, Conny Gysemans3, Alain Beschin1,2, Patrick De Baetselier1,2, and Jo A. Van Ginderachter1,2 1 Laboratory of Cellular and Molecular Immunology, Department of Molecular and Cellular Interactions, VIB, Brussels; 2 Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels; and 3 Laboratory of Experimental Medicine and Endocrinology, Department of Experimental Medicine, Katholieke Universiteit Leuven, Leuven, Belgium The induction of CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs) is an important immune-evading mechanism used by tumors. However, the exact nature and function of MDSCs remain elusive, especially because they constitute a heterogeneous population that has not yet been clearly defined. Here, we identified 2 distinct MDSC subfractions with clear morphologic, molecular, and functional differences. These fractions consisted of either mononuclear cells (MO-MDSCs), resembling inflammatory monocytes, or low-density polymorphonuclear cells (PMN-MDSCs), akin to immature neutrophils. Interestingly, both MO-MDSCs and PMN-MDSCs suppressed antigen-specific T-cell responses, albeit using distinct effector molecules and signaling pathways. Blocking IFN- or disrupting STAT1 partially impaired suppression by MO-MDSCs, for which nitric oxide (NO) was one of the mediators. In contrast, while IFN- was strictly required for the suppressor function of PMN-MDSCs, this did not rely on STAT1 signaling or NO production. Finally, MO-MDSCs were shown to be potential precursors of highly antiproliferative NO-producing mature macrophages. However, distinct tumors differentially regulated this inherent MO-MDSC differentiation program, indicating that this phenomenon was tumor driven. Overall, our data refine tumor-induced MDSC functions by uncovering mechanistically distinct MDSC subpopulations, potentially relevant for MDSC-targeted therapies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020