B-cell lymphomas differ in their responsiveness to CpG oligodeoxynucleotides

Details

Serval ID
serval:BIB_D8382B97E41B
Type
Article: article from journal or magazin.
Collection
Publications
Title
B-cell lymphomas differ in their responsiveness to CpG oligodeoxynucleotides
Journal
Clin Cancer Res
Author(s)
Jahrsdorfer B., Muhlenhoff L., Blackwell S. E., Wagner M., Poeck H., Hartmann E., Jox R., Giese T., Emmerich B., Endres S., Weiner G. J., Hartmann G.
ISSN
1078-0432 (Print)
ISSN-L
1078-0432
Publication state
Published
Issued date
2005
Volume
11
Number
4
Pages
1490-9
Language
english
Notes
Jahrsdorfer, Bernd
Muhlenhoff, Lars
Blackwell, Sue E
Wagner, Moritz
Poeck, Hendrik
Hartmann, Evelyn
Jox, Ralf
Giese, Thomas
Emmerich, Bertold
Endres, Stefan
Weiner, George J
Hartmann, Gunther
eng
Comparative Study
Research Support, Non-U.S. Gov't
2005/03/05 09:00
Clin Cancer Res. 2005 Feb 15;11(4):1490-9.
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.
Keywords
Adjuvants, Immunologic/pharmacology, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal/immunology, Antibodies, Monoclonal, Murine-Derived, Antigens, CD20/biosynthesis/immunology, Cell Proliferation/drug effects, Cell Survival/drug effects, Child, Child, Preschool, Female, Gene Expression Regulation, Neoplastic/drug effects, Humans, Lymphoma, B-Cell/*drug therapy/genetics/pathology, Male, Membrane Glycoproteins/genetics, Middle Aged, Oligodeoxyribonucleotides/*pharmacology, Plasmacytoma/drug therapy/genetics/pathology, RNA, Messenger/genetics/metabolism, Receptors, Cell Surface/genetics, Rituximab, Time Factors, Toll-Like Receptor 9, Toll-Like Receptors, Tumor Cells, Cultured
Pubmed
Open Access
Yes
Create date
14/07/2017 9:09
Last modification date
20/08/2019 15:57
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