Cover Image

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

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 p...

Full description

Saved in:
Bibliographic Details
Main Authors: Witzens-Harig, Mathias (Author) , Hose, Dirk (Author) , Jünger, Simone (Author) , Pfirschke, Christina (Author) , Khandelwal, Nisit (Author) , Umansky, Ludmila (Author) , Seckinger, Anja (Author) , Conrad, Heinke (Author) , Brackertz, Bettina (Author) , Rème, Thierry (Author) , Gueckel, Brigitte (Author) , Meißner, Tobias (Author) , Hundemer, Michael (Author) , Ho, Anthony Dick (Author) , Rossi, Jean-Francois (Author) , Neben, Kai (Author) , Bernhard, Helga (Author) , Goldschmidt, Hartmut (Author) , Klein, Bernard (Author) , Beckhove, Philipp (Author)
Format: Article (Journal)
Language:English
Published: April 19, 2013
In: Blood
Year: 2013, Volume: 121, Issue: 22, Pages: 4493-4503
ISSN:1528-0020
DOI:10.1182/blood-2012-05-429415
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood-2012-05-429415
Get full text
Author Notes:Mathias Witzens-Harig, Dirk Hose, Simone Jünger, Christina Pfirschke, Nisit Khandelwal, Ludmila Umansky, Anja Seckinger, Heinke Conrad, Bettina Brackertz, Thierry Rème, Brigitte Gueckel, Tobias Meißner, Michael Hundemer, Anthony D. Ho, Jean-Francois Rossi, Kai Neben, Helga Bernhard, Hartmut Goldschmidt, Bernard Klein, and Philipp Beckhove
Description
Summary: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.
Item Description:Gesehen am 18.11.2021
Physical Description:Online Resource
ISSN:1528-0020
DOI:10.1182/blood-2012-05-429415

Similar Items