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

2.50
Hdl Handle:
http://hdl.handle.net/10547/578801
Title:
Tumor cells in multiple myeloma patients inhibit myeloma-reactive T cells through carcinoembryonic antigen-related cell adhesion molecule-6
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
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.
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
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
Issue Date:
19-Apr-2013
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).
Appears in Collections:
Biomedicine and Nutrition Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorWitzens-Harig, Mathiasen
dc.contributor.authorHose, Dirken
dc.contributor.authorJunger, Simoneen
dc.contributor.authorPfirschke, Christinaen
dc.contributor.authorKhandelwal, Nisiten
dc.contributor.authorUmansky, Ludmillaen
dc.contributor.authorSeckinger, Anjaen
dc.contributor.authorConrad, Heinkeen
dc.contributor.authorBrackertz, Bettinaen
dc.contributor.authorReme, Thierryen
dc.contributor.authorGueckel, Brigitteen
dc.contributor.authorMeissner, Tobiasen
dc.contributor.authorHundemer, Michaelen
dc.contributor.authorHo, Anthony D.en
dc.contributor.authorRossi, Jean-Francoisen
dc.contributor.authorNeben, Kaien
dc.contributor.authorBernhard, Helgaen
dc.contributor.authorGoldschmidt, Hartmuten
dc.contributor.authorKlein, Bernarden
dc.contributor.authorBeckhove, Philippen
dc.date.accessioned2015-09-28T08:53:01Zen
dc.date.available2015-09-28T08:53:01Zen
dc.date.issued2013-04-19en
dc.identifier.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):4493en
dc.identifier.issn0006-4971en
dc.identifier.issn1528-0020en
dc.identifier.doi10.1182/blood-2012-05-429415en
dc.identifier.urihttp://hdl.handle.net/10547/578801en
dc.description.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.en
dc.description.sponsorshipThis 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).en
dc.language.isoenen
dc.publisherAmerican Society of Hematologyen
dc.relation.urlhttp://www.bloodjournal.org/cgi/doi/10.1182/blood-2012-05-429415en
dc.rightsArchived with thanks to Blooden
dc.subjecttumorsen
dc.subjecttumoursen
dc.subjecttumour cellsen
dc.subjectmultiple myelomaen
dc.subjectT-cellen
dc.subjectimmunotherapyen
dc.titleTumor cells in multiple myeloma patients inhibit myeloma-reactive T cells through carcinoembryonic antigen-related cell adhesion molecule-6en
dc.typeArticleen
dc.contributor.departmentUniversity Hospital of Heidelbergen
dc.contributor.departmentNationales Centrum für Tumorerkrankungenen
dc.contributor.departmentGerman Cancer Research Centeren
dc.contributor.departmentTechnische Universität, Münchenen
dc.contributor.departmentInstitut National de la Santé et de la Recherche Médicaleen
dc.contributor.departmentInstitute of Research in Biotherapyen
dc.contributor.departmentUnité de Formation et de Recherche Médecineen
dc.contributor.departmentUniversity Hospital of Tübingenen
dc.contributor.departmentKlinikum Darmstadt Gesellschaft mit beschränkter Haftungen
dc.identifier.journalBlooden
All Items in UOBREP are protected by copyright, with all rights reserved, unless otherwise indicated.