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

Magdalena Hagn; Sue E Blackwell; Thamara Beyer; Verena Ebel; Dorit Fabricius; Stefanie Lindner; Stefan Stilgenbauer; Thomas Simmet; Constantine Tam; Paul Neeson; Joseph A Trapani; Hubert Schrezenmeier; George J Weiner; Bernd Jahrsdörfer

doi:10.1093/intimm/dxu001

Back

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

Journal article

Open access

Peer reviewed

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

Magdalena Hagn, Sue E Blackwell, Thamara Beyer, Verena Ebel, Dorit Fabricius, Stefanie Lindner, Stefan Stilgenbauer, Thomas Simmet, Constantine Tam, Paul Neeson, …

International immunology, Vol.26(7), pp.383-395

07/2014

DOI: 10.1093/intimm/dxu001

PMCID: PMC4133571

PMID: 24497611

Files and links (1)

url

https://doi.org/10.1093/intimm/dxu001View

Published (Version of record) Open Access

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.

Perforin - genetics

Apoptosis - drug effects

Humans

Middle Aged

Male

T-Box Domain Proteins - immunology

Granzymes - genetics

Leukemia, Lymphocytic, Chronic, B-Cell - genetics

Antigen-Presenting Cells - pathology

Chemokine CXCL10 - immunology

Aged, 80 and over

Female

Granzymes - immunology

Perforin - immunology

B-Lymphocytes - pathology

Interleukins - pharmacology

Cytotoxicity, Immunologic - drug effects

Leukemia, Lymphocytic, Chronic, B-Cell - immunology

Signal Transduction

Antigen-Presenting Cells - drug effects

Immunophenotyping

Gene Expression Regulation, Leukemic

Recombinant Proteins - pharmacology

Antigen-Presenting Cells - immunology

T-Box Domain Proteins - genetics

Leukemia, Lymphocytic, Chronic, B-Cell - pathology

B-Lymphocytes - drug effects

B-Lymphocytes - immunology

Chemokine CXCL10 - genetics

Lymphocyte Activation - drug effects

Aged

Primary Cell Culture

Oligodeoxyribonucleotides - pharmacology

Details

Title: Subtitle: B-CLL cells acquire APC- and CTL-like phenotypic characteristics after stimulation with CpG ODN and IL-21
Creators: Magdalena Hagn - Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne 3002, Australia
Sue E Blackwell - Department of Internal Medicine, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA
Thamara Beyer - Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg - Hessen and Institute of Transfusion Medicine
Verena Ebel - Institute of Pharmacology of Natural Products and Clinical Pharmacology
Dorit Fabricius - Department of Pediatrics and
Stefanie Lindner - Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg - Hessen and Institute of Transfusion Medicine
Stefan Stilgenbauer - Department of Internal Medicine III, Ulm University, Ulm 89081, Germany
Thomas Simmet - Institute of Pharmacology of Natural Products and Clinical Pharmacology
Constantine Tam - Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne 3002, Australia
Paul Neeson - Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne 3002, Australia
Joseph A Trapani - Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne 3002, Australia
Hubert Schrezenmeier - Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg - Hessen and Institute of Transfusion Medicine
George J Weiner - Department of Internal Medicine, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA
Bernd Jahrsdörfer - Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg - Hessen and Institute of Transfusion Medicine, bernd.jahrsdoerfer@uni-ulm.de
Resource Type: Journal article
Publication Details: International immunology, Vol.26(7), pp.383-395
DOI: 10.1093/intimm/dxu001
PMID: 24497611
PMCID: PMC4133571
ISSN: 0953-8178
eISSN: 1460-2377
Grant note: P50 CA97274 / NCI NIH HHS
Language: English
Date published: 07/2014
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Holden Comprehensive Cancer Center; Internal Medicine
Record Identifier: 9984094320902771

Metrics

28 Record Views

14 Times Cited - Web of Science

See more details