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dc.contributor.authorSong, Wen_US
dc.contributor.authorTai, Y-Ten_US
dc.contributor.authorTian, Zen_US
dc.contributor.authorHideshima, Ten_US
dc.contributor.authorChauhan, Den_US
dc.contributor.authorNanjappa, Pen_US
dc.contributor.authorExley, M Aen_US
dc.contributor.authorAnderson, K Cen_US
dc.contributor.authorMunshi, N Cen_US
dc.date.accessioned2014-03-11T02:49:30Z
dc.date.issued2013en_US
dc.identifier.citationSong, W, Y-T Tai, Z Tian, T Hideshima, D Chauhan, P Nanjappa, M A Exley, K C Anderson, and N C Munshi. 2013. “HDAC Inhibition by LBH589 Affects Phenotype and Function of Human Myeloid Dendritic Cells.” Leukemia 25 (1): 10.1038/leu.2010.244. doi:10.1038/leu.2010.244. http://dx.doi.org/10.1038/leu.2010.244.en
dc.identifier.issn0887-6924en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11879136
dc.description.abstractLBH589 is a novel pan-HDAC inhibitor which has potent antitumor activity in multiple myeloma and other hematologic malignancies. However, its impact on immune system has not been defined. We here evaluated the effects of LBH589 on human myeloid dendritic cells (DCs) at clinically relevant concentrations. Exposure to LBH589 affected the surface molecule expression on immature and mature DCs, associated with DC maturation (CD83↓), antigen presentation (HLA-ABC↓), and T cell co-stimulation (CD40↓ and CD86↑). LBH589 decreased both protein and polysaccharide antigen uptake capacities by DCs. Importantly, LBH589 impaired DCs function to stimulate antigen-specific immune responses, resulting in the significant reduction of invariant NKT cell (CD1d-restricted) and T cell (MHC-restricted) activation in innate and adaptive immunity. LBH589 also significantly repressed the production of IL-6, IL-10, IL-12p70, IL-23 and TNF-α by TLR3 and TLR4-induced DCs activation, indicating an important role of HDAC activity in immune regulation and inflammation. RelB, a component of NF-κB signaling pathway, was the key component regulated by HDAC inhibition in DCs. Together, our preclinical study demonstrates that LBH589 significantly impairs phenotype and function of DCs, indicating a need for monitoring the immune status in patients receiving HDAC inhibitor therapy. It also provides a rationale to evaluate LBH589 activity for the treatment of inflammation.en
dc.language.isoen_USen
dc.relation.isversionofdoi:10.1038/leu.2010.244en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839585/pdf/en
dash.licenseLAAen_US
dc.subjectHistone Deacetylase Inhibitoren
dc.subjectLBH589en
dc.subjectdendritic cellsen
dc.subjectT cellsen
dc.subjectinvariant NKT cellsen
dc.subjecten
dc.titleHDAC Inhibition by LBH589 Affects Phenotype and Function of Human Myeloid Dendritic Cellsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalLeukemiaen
dc.date.available2014-03-11T02:49:30Z
dc.identifier.doi10.1038/leu.2010.244*


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