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B-CLL cells acquire APC- and CTL-like phenotypic characteristics after stimulation with CpG ODN and IL-21.

Authors
  • 1
  • 2
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  • 5
  • 3
  • 6
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  • 1
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  • 1 Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne 3002, Australia. , (Australia)
  • 2 Department of Internal Medicine, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA.
  • 3 Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg - Hessen and Institute of Transfusion Medicine.
  • 4 Institute of Pharmacology of Natural Products and Clinical Pharmacology.
  • 5 Department of Pediatrics and.
  • 6 Department of Internal Medicine III, Ulm University, Ulm 89081, Germany. , (Germany)
  • 7 Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg - Hessen and Institute of Transfusion Medicine, [email protected]
Type
Published Article
Journal
International Immunology
1460-2377
Publisher
Oxford University Press
Publication Date
Volume
26
Issue
7
Pages
383–395
Identifiers
DOI: 10.1093/intimm/dxu001
PMID: 24497611
Source
Medline
Keywords
License
Unknown

Abstract

CpG oligodeoxynucleotides (CpG) and IL-21 are two promising agents for the treatment of B-cell chronic lymphocytic leukemia (B-CLL). Recently, we reported that the combination of CpG and IL-21 (CpG/IL-21) can induce granzyme B (GrB)-dependent apoptosis in B-CLL cells. Here, we demonstrate that treatment of B-CLL cells with CpG and IL-21 results in the development of antigen-presenting cell (APC)-like cells with cytotoxic features. These properties eventually give rise to B-CLL cell apoptosis, independently of their cytogenetic phenotype, whereas normal B-cell survival is not negatively affected by CpG/IL-21. APC- and CTL-typical molecules found to be up-regulated in CpG/IL-21-stimulated B-CLL cells include GrB, perforin, T-bet, monokine-induced by IFN-γ and IFN-γ-inducible protein 10 (IP-10), as well as molecules important for cell adhesion, antigen cross-presentation and costimulation. Also induced are molecules involved in GrB induction, trafficking and processing, whereas the GrB inhibitor Serpin B9 [formerly proteinase inhibitor-9 (PI-9)] is down-modulated by CpG/IL-21. In conclusion, CpG/IL-21-stimulated B-CLL cells acquire features that are reminiscent of killer dendritic cells, and which result in enhanced immunogenicity, cytotoxicity and apoptosis. Our results provide novel insights into the aberrant immune state of B-CLL cells and may establish a basis for the development of an innovative cellular vaccination approach in B-CLL.

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