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Blood, 15 April 2004, Vol. 103, No. 8, pp. 3122-3130. Prepublished online as a Blood First Edition Paper on December 4, 2003; DOI 10.1182/blood-2003-07-2500. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-07-2500v1 103/8/3122    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 Demanet, C. Articles by Ferrone, S. Search for Related Content PubMed PubMed Citation Articles by Demanet, C. Articles by Ferrone, S. Related Collections Immunobiology Neoplasia Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Down-regulation of HLA-A and HLA-Bw6, but not HLA-Bw4, allospecificities in leukemic cells: an escape mechanism from CTL and NK attack? Christian Demanet, Arend Mulder, Veronique Deneys, Maria J. Worsham, Piet Maes, Frans H. Claas, and Soldano Ferrone From the HLA Laboratory, Academic Hospital VUB, Brussels, Belgium; the Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands; the Department of Immunohematology, Université Catholique de Louvain, Brussels, Belgium; the Department of Pathology, Henry Ford Hospital, Detroit, MI; and the Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY. Human leukocyte antigen (HLA) class I antigen defects may have a negative impact on the growing application of T-cell–based immunotherapeutic strategies for treatment of leukemia. Therefore in the present study, taking advantage of a large panel of HLA class I allele–specific human monoclonal antibodies, we have compared HLA class I antigen expression on leukemic cells with that on autologous and allogeneic normal cells. Down-regulation of HLA-A and/or -B allospecificities was present in the majority of the patients studied. However, down-regulation did not affect all HLA class I alleles uniformly, but was almost exclusively restricted to HLA-A allospecificities and to HLA-B allospecificities which belong to the HLA-Bw6 group. The latter allospecificities, at variance from those that belong to the HLA-Bw4 group, do not modulate the interactions of leukemic cells with natural killer (NK) cells. Therefore, our results suggest that the selective down-regulation of HLA-A and HLA-Bw6 allospecificities associated with HLA-Bw4 preservation provides leukemic cells with an escape mechanism not only from cytotoxic T lymphocytes (CTLs), but also from NK cells. As a result T-cell–based immunotherapeutic strategies for leukemia should utilize HLA-Bw4 alloantigens as restricting elements since a selective HLA-Bw4 allele loss would provide leukemic cells with an escape mechanism from CTLs, but would increase their susceptibility to NK cell–mediated lysis. (Blood. 2004;103:3122-3130) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Baessler, M. Krusch, B. J. Schmiedel, M. Kloss, K. M. Baltz, A. Wacker, H. M. Schmetzer, and H. R. Salih Glucocorticoid-Induced Tumor Necrosis Factor Receptor-Related Protein Ligand Subverts Immunosurveillance of Acute Myeloid Leukemia in Humans Cancer Res., February 1, 2009; 69(3): 1037 - 1045. [Abstract] [Full Text] [PDF] J. North, I. Bakhsh, C. Marden, H. Pittman, E. Addison, C. Navarrete, R. Anderson, and M. W. Lowdell Tumor-Primed Human Natural Killer Cells Lyse NK-Resistant Tumor Targets: Evidence of a Two-Stage Process in Resting NK Cell Activation J. Immunol., January 1, 2007; 178(1): 85 - 94. [Abstract] [Full Text] [PDF]

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