Fri, 04 Jul 2008 23:40:41 BST CiteULike: AlfonsoVicenteSuarez's Wagner http://www.citeulike.org/user/AlfonsoVicenteSuarez/author/Wagner CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/2781997 <i>Cancer Res, Vol. 65, No. 14. (15 July 2005), pp. 6409-6417.</i><br /><br />BCR/ABL fusion gene, encoding a paradigmatic tyrosine kinase involved in chronic myelogenous leukemia (CML), can modulate the expression of genes involved in natural killer (NK) cell target recognition. Recent reports outline the role of allogeneic antileukemic NK effectors in the graft-versus-leukemia effect but the regulation of NK cell activation in the setting of graft-versus-leukemia effect remains unknown. Here we show that dendritic cells derived from monocytes of CML patients are selectively endowed with NK cell stimulatory capacity in vitro. We further show, using a gene transfer approach in mouse bone marrow progenitors, that ABL/ABL is necessary to promote dendritic cell-mediated NK cell activation. The dendritic cell/NK cell cross-talk in ABL/ABL-induced CML seems unique because JunB or IFN consensus sequence binding protein loss of functions, associated with other myeloproliferative disorders, do not promote dendritic cell-mediated NK cell activation. NK cell activation by leukemic dendritic cells involves NKG2D activating receptors and is blocked by imatinib mesylate. Indeed, ABL/ABL translocation enhances the expression levels of the NKG2D ligands on dendritic cells, which is counteracted by imatinib mesylate. Altogether, the clonal ABL/ABL dendritic cells display the unique and selective ability to activate NK cells and may participate in the NK cell control of CML. This study also highlights the deleterious role of imatinib mesylate at the dendritic cell level for NK cell activation. 10.1158/0008-5472.CAN-04-2675 BCR/ABL Promotes Dendritic Cell-Mediated Natural Killer Cell Activation Magali Terme Christophe Borg Francois Guilhot Carole Masurier Caroline Flament Erwin Wagner Sophie Caillat-Zucman Alain Bernheim Ali Turhan Anne Caignard Laurence Zitvogel doi:10.1158/0008-5472.CAN-04-2675 Cancer Res, Vol. 65, No. 14. (15 July 2005), pp. 6409-6417. 2008-05-09T23:33:06-00:00 2005 Cancer Res 65 14 6409 6417 ra rae-1 http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1452955 <i>Immunity, Vol. 12, No. 6. (June 2000), pp. 721-727.</i><br /><br />Here we describe a family of GPI-anchored cell surface proteins that function as ligands for the mouse activating NKG2D receptor. These molecules are encoded by the retinoic acid early inducible (RAE-1) and H60 minor histocompatibility antigen genes on mouse chromosome 10 and show weak homology with MHC class I. Expression of the NKG2D ligands is low or absent on normal, adult tissues; however, they are constitutively expressed on some tumors and upregulated by retinoic acid. Ectopic expression of RAE-1 and H60 confers target susceptibility to NK cell attack. These studies identify a family of ligands for the activating NKG2D receptor on NK and T cells, which may play an important role in innate and adaptive immunity. Retinoic acid early inducible genes define a ligand family for the activating NKG2D receptor in mice. A Cerwenka AB Bakker T McClanahan J Wagner J Wu JH Phillips LL Lanier Immunity, Vol. 12, No. 6. (June 2000), pp. 721-727. 2007-07-12T20:32:30-00:00 2000 Immunity 1074-7613 12 6 721 727 ra rae-1 http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1420055 <i>Cancer Res, Vol. 63, No. 19. (1 October 2003), pp. 6478-6487.</i><br /><br />The antitumor activity of IFN-alpha is well established. However, the role of the plasmacytoid dendritic cell (PDC), the major producer of IFN-alpha upon viral infection, in tumor biology is unknown. We sought to study the presence and function of PDC in a human solid tumor. Here, we demonstrate that PDCs infiltrate tumor tissue of patients with head and neck squamous cell carcinoma (HNSCC). Functional activity of PDC was examined by using CpG motif containing oligonucleotides, a defined microbial stimulus for PDCs (recognized via toll-like receptor 9). We found that HNSCC diminished the ability of PDC to produce IFN-alpha in response to CpG motif containing oligonucleotide. Tumor-induced down-regulation of toll-like receptor 9 was identified as one mechanism likely contributing to impaired PDC function within the tumor environment. In tumor-draining lymph nodes, suppression of CpG-induced IFN-alpha production was less pronounced than in single-cell suspensions of primary tumor tissue. In these lymph nodes, CpG-induced IFN-alpha production was associated with increased levels of interferon-induced protein 10 and IFN-gamma and activation of CD4 and CD8 T cells. These results show for the first time the presence of PDCs in human solid tumor tissue and that tumors suppress the capacity of PDCs to produce IFN-alpha. PDCs, which in the absence of appropriate stimulation are reported to promote regulatory CD8 T cells, may contribute to an impaired T-cell-mediated immune response in HNSCC. Identification and Functional Analysis of Tumor-Infiltrating Plasmacytoid Dendritic Cells in Head and Neck Cancer Evelyn Hartmann Barbara Wollenberg Simon Rothenfusser Moritz Wagner Daniela Wellisch Brigitte Mack Thomas Giese Olivier Gires Stefan Endres Gunther Hartmann Cancer Res, Vol. 63, No. 19. (1 October 2003), pp. 6478-6487. 2007-06-28T16:24:06-00:00 2003 Cancer Res 63 19 6478 6487 tumor-dcs http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1420040 <i>Nat Med, Vol. 10, No. 9. (2004), pp. 950-958.</i> Tumor-infiltrating dendritic cell precursors recruited by a [beta]-defensin contribute to vasculogenesis under the influence of Vegf-A Jose Conejo-Garcia Fabian Benencia Maria-Cecilia Courreges Eugene Kang Alisha Mohamed-Hadley Ronald Buckanovich David Holtz Ann Jenkins Hana Na Lin Zhang Daniel Wagner Dionyssios Katsaros Richard Caroll George Coukos doi:10.1038/nm1097 Nat Med, Vol. 10, No. 9. (2004), pp. 950-958. 2007-06-28T16:15:22-00:00 2004 Nat Med 10 9 950 958 tumor-dcs