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 Blood, 15 November 2008, Vol. 112, No. 10, pp. 4080-4089.
Prepublished online as a Blood First Edition Paper on August 27, 2008; DOI 10.1182/blood-2008-03-143776.

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IMMUNOBIOLOGY

Mononuclear myeloid-derived "suppressor" cells express RAE-1 and activate natural killer cells

Norman Nausch1, Ioanna E. Galani1, Eva Schlecker1, and Adelheid Cerwenka1

1 Division of Innate Immunity, German Cancer Research Center, Heidelberg, Germany

Myeloid-derived suppressor cells (MDSCs) accumulate in cancer patients and tumor-bearing mice and potently suppress T-cell activation. In this study, we investigated whether MDSCs regu-late natural killer (NK)–cell function. We discovered that mononuclear Gr-1+CD11b+F4/80+ MDSCs isolated from RMA-S tumor-bearing mice do not suppress, but activate NK cells to produce high amounts of IFN-{gamma}. Gr-1+CD11b+F4/80+ MDSCs isolated from tumor-bearing mice, but not myeloid cells from naive mice, expressed the ligand for the activating receptor NKG2D, RAE-1. NK-cell activation by MDSCs depended partially on the interaction of NKG2D on NK cells with RAE-1 on MDSCs. NK cells eliminated Gr-1+CD11b+F4/80+ MDSCs in vitro and upon adoptive transfer in vivo. Finally, depletion of Gr-1+ cells that comprise MDSCs confirmed their protective role against the NK-sensitive RMA-S lymphoma in vivo. Our study reveals that MDSCs do not suppress all aspects of antitumor immune responses and defines a novel, unexpected activating role of MDSCs on NK cells. Thus, our results have great impact on the design of immune therapies against cancer aiming at the manipulation of MDSCs.


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Myeloid-Derived Suppressor Cells: Linking Inflammation and Cancer
J. Immunol., April 15, 2009; 182(8): 4499 - 4506.
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