Tumor cells in multiple myeloma patients inhibit myeloma-reactive T cells through carcinoembryonic antigen-related cell adhesion molecule-6
Ho, Anthony D.
AffiliationUniversity 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
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AbstractAlthough 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.
CitationWitzens-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
PublisherAmerican Society of Hematology
SponsorsThis 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).