Document Detail


Enhanced cross-priming of naive CD8+ T cells by dendritic cells treated by the IMiDs® immunomodulatory compounds lenalidomide and pomalidomide.
MedLine Citation:
PMID:  23374145     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The IMiDs(®) immunomodulatory compounds lenalidomide and pomalidomide are agents with anti-inflammatory, immunomodulatory and anti-cancer activity. An excellent success rate has been shown for multiple myeloma in phase I/II clinical trials leading to Food and Drug Administration approval of lenalidomide. One mechanism by which these drugs could enhance anti-tumour immunity may be through enhanced dendritic cell (DC) function. Thalidomide, a compound structurally related to lenalidomide and pomalidomide, is known to enhance DC function, and we have investigated whether its analogues, pomalidomide and lenalidomide, also have functional effects on DCs. We used mouse bone marrow-derived DCs treated with 5 or 10 μm pomalidomide, or lenalidomide from day 1 of culture. Treatment with IMiD(®) immunomodulatory compounds increased expression of Class I (H2-Kb), CD86, and pomalidomide also increased Class II (I-Ab) expression in bone marrow-derived DCs, as measured by flow cytometry. Fluorescent bead uptake was increased by up to 45% when DCs were treated with 5 or 10 μm pomalidomide or lenalidomide compared with non-treated DCs. Antigen presentation assays using DCs primed with ovalbumin, and syngeneic T cells from transgenic OTI and OTII mice (containing MHC restricted, ovalbumin-specific, T cells) showed that both pomalidomide and lenalidomide effectively increased CD8(+) T-cell cross-priming (by up to 47%) and that pomalidomide alone was effective in increasing CD4(+) T-cell priming (by 30%). Our observations suggest that pomalidomide and lenalidomide enhance tumour antigen uptake by DCs with an increased efficacy of antigen presentation, indicating a possible use of these drugs in DC vaccine therapies.
Authors:
Jake Y Henry; Marie-Christine Labarthe; Brendan Meyer; Prokar Dasgupta; Angus G Dalgleish; Christine Galustian
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Immunology     Volume:  139     ISSN:  1365-2567     ISO Abbreviation:  Immunology     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-14     Completed Date:  2013-08-19     Revised Date:  2014-07-01    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  England    
Other Details:
Languages:  eng     Pagination:  377-85     Citation Subset:  IM    
Copyright Information:
© 2013 John Wiley & Sons Ltd.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigen Presentation / drug effects,  immunology
Antigens, Neoplasm / immunology
CD8-Positive T-Lymphocytes / immunology*
Cells, Cultured
Cross-Priming / immunology*
Dendritic Cells / drug effects*,  immunology
Female
Immunologic Factors / immunology,  pharmacology
Lymphocyte Activation / drug effects
Mice
Mice, Inbred C57BL
Ovalbumin / immunology
Thalidomide / analogs & derivatives*,  immunology,  pharmacology
Grant Support
ID/Acronym/Agency:
MR/J006742/1//Medical Research Council
Chemical
Reg. No./Substance:
0/Antigens, Neoplasm; 0/Immunologic Factors; 191732-72-6/lenalidomide; 4Z8R6ORS6L/Thalidomide; 9006-59-1/Ovalbumin; D2UX06XLB5/pomalidomide
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