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Ly49G2 receptor blockade reduces tumor burden in a leukemia model but not in a solid tumor model
Authors:Melissa A Barber  Tong Zhang  Bethany A Gagne  Jo A Van Ginderachter  Patrick De Baetselier  Charles L Sentman
Institution:(1) Department of Microbiology and Immunology, Dartmouth Medical School, 6W Borwell Bldg, One Medical Center Dr, Lebanon, NH 03756, USA;(2) Lab of Cellular and Molecular Immunology, Department of Molecular and Cellular Interactions, VIB, Brussels, Belgium;(3) Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium
Abstract:Background NK cell activity is regulated in part by inhibitory receptors that bind to MHC class I molecules. It is possible to enhance NK cell cytotoxicity against tumor cells by preventing the interaction of these inhibitory receptors with their MHC class I ligands. Results In this study, we determined that Ly49G2 is an inhibitory receptor in AKR mice for self-MHC class I, and AKR Ly49G2 has an identical sequence to BALB/c Ly49G2. Blockade of Ly49G2 receptors in vivo resulted in decreased growth of BW-Sp3 lymphoma cells when the tumor cells were given i.v. but not when the tumor cells were inoculated into the flank forming a solid tumor. However, NK cells were involved in inhibiting the growth of BW-Sp3 tumor cells in the flank. Conclusion These data demonstrate that the effectiveness of inhibitory receptor blockade depends upon the tissue location of the tumor cells.
Keywords:Natural Killer Cells  Tumor Immunity  Immunotherapy  AKR  Lymphoma
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