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    Tumor cells in multiple myeloma patients inhibit myeloma-reactive T cells through carcinoembryonic antigen-related cell adhesion molecule-6

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    Authors
    Witzens-Harig, Mathias
    Hose, Dirk
    Junger, Simone
    Pfirschke, Christina
    Khandelwal, Nisit
    Umansky, Ludmilla
    Seckinger, Anja
    Conrad, Heinke
    Brackertz, Bettina
    Reme, Thierry
    Gueckel, Brigitte
    Meissner, Tobias
    Hundemer, Michael
    Ho, Anthony D.
    Rossi, Jean-Francois
    Neben, Kai
    Bernhard, Helga
    Goldschmidt, Hartmut
    Klein, Bernard
    Beckhove, Philipp
    Show allShow less
    Affiliation
    University Hospital of Heidelberg
    Nationales Centrum für Tumorerkrankungen
    German Cancer Research Center
    Technische Universität, München
    Institut National de la Santé et de la Recherche Médicale
    Institute of Research in Biotherapy
    Unité de Formation et de Recherche Médecine
    University Hospital of Tübingen
    Klinikum Darmstadt Gesellschaft mit beschränkter Haftung
    Issue Date
    2013-04-19
    Subjects
    tumors
    tumours
    tumour cells
    multiple myeloma
    T-cell
    immunotherapy
    
    Metadata
    Show full item record
    Abstract
    Although functionally competent cytotoxic, T cells are frequently observed in malignant diseases, they possess little ability to react against tumor cells. This phenomenon is particularly apparent in multiple myeloma. We here demonstrate that cytotoxic T cells reacted against myeloma antigens when presented by autologous dendritic cells, but not by myeloma cells. We further show by gene expression profiling and flow cytometry that, similar to many other malignant tumors, freshly isolated myeloma cells expressed several carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) at varying proportions. Binding and crosslinking of CEACAM-6 by cytotoxic T cells inhibited their activation and resulted in T-cell unresponsiveness. Blocking of CEACAM-6 on the surface of myeloma cells by specific monoclonal antibodies or CEACAM-6 gene knock down by short interfering RNA restored T-cell reactivity against malignant plasma cells. These findings suggest that CEACAM-6 plays an important role in the regulation of CD8+ T-cell responses against multiple myeloma; therefore, therapeutic targeting of CEACAM-6 may be a promising strategy to improve myeloma immunotherapy.
    Citation
    Witzens-Harig, M., Hose, D., Junger, S., Pfirschke, C., Khandelwal, N., Umansky, L., Seckinger, A., Conrad, H., Brackertz, B., Rème, T., Gueckel, B., Meißner, T., Hundemer, M., Ho, A.D., Rossi, J.-F., Neben, K., Bernhard, H., Goldschmidt, H., Klein, B., Beckhove, P. (2013) 'Tumor cells in multiple myeloma patients inhibit myeloma-reactive T cells through carcinoembryonic antigen-related cell adhesion molecule-6'. Blood 121 (22):4493
    Publisher
    American Society of Hematology
    Journal
    Blood
    URI
    http://hdl.handle.net/10547/578801
    DOI
    10.1182/blood-2012-05-429415
    Additional Links
    http://www.bloodjournal.org/cgi/doi/10.1182/blood-2012-05-429415
    Type
    Article
    Language
    en
    ISSN
    0006-4971
    1528-0020
    Sponsors
    This study was supported in part by the Deutsches Krebsforschungszentrum-Bayer Health Care Alliance and by the Deutsche Forschungsgemeinschaft, Bonn, Germany, including the SFB/TRR79; the Dietmar Hopp Foundation, St. Leon-Rot, Germany; the University of Heidelberg, Germany; the Ligue Nationale Contre Le Cancer, Paris, France; and the 7th framework program of the European Union (OverMyR).
    ae974a485f413a2113503eed53cd6c53
    10.1182/blood-2012-05-429415
    Scopus Count
    Collections
    Biomedicine and Nutrition Research Group

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