Journal article
B-cell lymphomas differ in their responsiveness to CpG oligodeoxynucleotides
Clinical cancer research, Vol.11(4), pp.1490-1499
2005
DOI: 10.1158/1078-0432.CCR-04-1890
PMID: 15746051
Abstract
Human B cells detect CpG motifs within microbial DNA via TLR9. Synthetic CpG oligodeoxynucleotides are currently being tested in clinical trials for the therapy of different types of B cell non-Hodgkin's lymphoma. However, there is only limited information on the CpG oligodeoxynucleotide sensitivity of primary malignant B cells of different non-Hodgkin's lymphoma entities. Here we found that most B-cell malignancies except plasmacytoma respond to CpG oligodeoxynucleotides by up-regulating expression of costimulatory and antigen-presenting molecules, by increasing expression of CD20, and by proliferation. In an in vitro analysis of 41 individual patient-derived primary tumor samples, B-cell chronic lymphocytic leukemia (B-CLL) and marginal zone lymphoma showed the strongest activation upon stimulation with CpG oligodeoxynucleotides. Small lymphocytic lymphoma, follicular lymphoma, mantle cell lymphoma, and large cell lymphoma showed an intermediate response. Consistent with CpG oligodeoxynucleotides sensitivity, TLR9 mRNA was present in B-CLL but absent in plasmacytoma. Although CpG oligodeoxynucleotides induced proliferation in all CpG oligodeoxynucleotide-sensitive types of B-cell malignancies, proliferation was weaker than in normal B cells and at least for B-CLL was followed by increased apoptosis. In conclusion, B-cell malignancies show significant differences in their responsiveness to CpG oligodeoxynucleotides. Focusing clinical studies on patients with highly CpG oligodeoxynucleotide-sensitive B-cell malignancies may improve the clinical outcome of such trials.
Details
- Title: Subtitle
- B-cell lymphomas differ in their responsiveness to CpG oligodeoxynucleotides
- Creators
- Bernd JAHRSDORFER - Holden Comprehensive Cancer Center and Department of Internal Medicine, University of Iowa, Iowa City, United StatesLars MÜHLENHOFF - Division of Clinical Pharmacology, University of Munich, Munich, GermanyGeorge J WEINER - Holden Comprehensive Cancer Center and Department of Internal Medicine, University of Iowa, Iowa City, United StatesGunther HARTMANN - Division of Clinical Pharmacology, University of Munich, Munich, GermanySue E BLACKWELL - Holden Comprehensive Cancer Center and Department of Internal Medicine, University of Iowa, Iowa City, United StatesMoritz WAGNER - Division of Clinical Pharmacology, University of Munich, Munich, GermanyHendrik POECK - Division of Clinical Pharmacology, University of Munich, Munich, GermanyEvelyn HARTMANN - Department of Otorhinolaryngology, University of Munich, Munich, GermanyRalf JOX - Division of Clinical Pharmacology, University of Munich, Munich, GermanyThomas GIESE - Institute of Immunology, University of Heidelberg, Heidelberg, GermanyBertold EMMERICH - Department of Internal Medicine, Division of Hematology, University of Munich, Munich, GermanyStefan ENDRES - Division of Clinical Pharmacology, University of Munich, Munich, Germany
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.11(4), pp.1490-1499
- DOI
- 10.1158/1078-0432.CCR-04-1890
- PMID
- 15746051
- NLM abbreviation
- Clin Cancer Res
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Publisher
- American Association for Cancer Research
- Language
- English
- Date published
- 2005
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Holden Comprehensive Cancer Center; Internal Medicine
- Record Identifier
- 9984094520402771
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