Either interleukin-12 or interferon-gamma can correct the dendritic cell defect induced by transforming growth factor beta(1) in patients with myeloma

Brown, R, Murray, A, Pope, B, Sze, DM, Gibson, J, Ho, PJ, Hart, D and Joshua, D (2004) Either interleukin-12 or interferon-gamma can correct the dendritic cell defect induced by transforming growth factor beta(1) in patients with myeloma. British Journal of Haematology, 125 6: 743-748. doi:10.1111/j.1365-2141.2004.04984.x


Author Brown, R
Murray, A
Pope, B
Sze, DM
Gibson, J
Ho, PJ
Hart, D
Joshua, D
Title Either interleukin-12 or interferon-gamma can correct the dendritic cell defect induced by transforming growth factor beta(1) in patients with myeloma
Journal name British Journal of Haematology   Check publisher's open access policy
ISSN 0007-1048
Publication date 2004
Sub-type Article (original research)
DOI 10.1111/j.1365-2141.2004.04984.x
Volume 125
Issue 6
Start page 743
End page 748
Total pages 6
Editor F. Cotter
I. Hann
J. Reilly
Place of publication UK
Publisher Blackwell Publishing Ltd
Collection year 2004
Language eng
Subject C1
320206 Tumor Immunology
730108 Cancer and related disorders
Abstract The poor response to immunotherapy in patients with multiple myeloma (MM) indicates that a better understanding of any defects in the immune response in these patients is required before effective therapeutic strategies can be developed. Recently we reported that high potency (CMRF44(+)) dendritic cells (DC) in the peripheral blood of patients with MM failed to significantly up-regulate the expression of the B7 co-stimulatory molecules, CD80 and CD86, in response to an appropriate signal from soluble trimeric human CD40 ligand. This defect was caused by transforming growth factor beta(1) (TGFbeta(1)) and interleukin (IL)-10, produced by malignant plasma cells, and the defect was neutralized in vitro with anti-TGFbeta(1). As this defect could impact on immunotherapeutic strategies and may be a major cause of the failure of recent trials, it was important to identify a more clinically useful agent that could correct the defect in vivo. In this study of 59 MM patients, the relative and absolute numbers of blood DC were only significantly decreased in patients with stage III disease and CD80 up-regulation was reduced in both stage I and stage III. It was demonstrated that both IL-12 and interferon-gamma neutralized the failure to stimulate CD80 up-regulation by huCD40LT in vitro. IL-12 did not cause a change in the distribution of DC subsets that were predominantly myeloid (CD11c+ and CDw123-) suggesting that there would be a predominantly T-helper cell type response. The addition of IL-12 or interferon-gamma to future immunotherapy trials involving these patients should be considered.
Keyword Hematology
Dendritic Cells
Multiple Myeloma
Interleukin-12
Transforming Growth Factor Beta
Immunotherapy
Colony-stimulating Factor
Class-ii Compartments
Multiple-myeloma
Human Blood
Vaccination
Populations
Expression
Protein
System
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2005 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Wed, 15 Aug 2007, 05:16:47 EST