title: Inhibition of cell-mediated immunity by the histone deacetylase inhibitor vorinostat: implications for therapy of cutaneous T-cell lymphoma.
abstract: Several histone deacetylase inhibitors (HDACi), including vorinostat, have been approved for the therapy of cutaneous T-cell lymphoma (CTCL). Emerging data suggest that HDACi may exert immune suppressive effects which would be disadvantageous for therapy of CTCL. We describe a patient with Sezary syndrome who was monitored for drug-induced immunosuppression while undergoing treatment with vorinostat. Analysis of the patient's natural killer cell function before and after initiation of treatment confirmed inhibition of this important cell-mediated immune function. In addition, the in vitro effects of vorinostat on the immunity of healthy volunteers confirmed that this class of drug can profoundly suppress multiple arms of the cellular immune response. These findings raise concerns of increased susceptibility to infection in this high-risk population.
authors.affiliation: Department of Dermatology, University of Pennsylvania and the Wistar Institute, Philadelphia, PA 19104, USA. sasha.stephen@uphs.upenn.edu
authors.forename: Sasha
authors.initials: S
authors.lastname: Stephen
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Morrissey
authors.forename: Bernice M
authors.initials: BM
authors.lastname: Benoit
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Kim
authors.forename: Carmela C
authors.initials: CC
authors.lastname: Vittorio
authors.forename: Sunita D
authors.initials: SD
authors.lastname: Nasta
authors.forename: Louise C
authors.initials: LC
authors.lastname: Showe
authors.forename: Maria
authors.initials: M
authors.lastname: Wysocka
authors.forename: Alain H
authors.initials: AH
authors.lastname: Rook
mesh_terms: D000368:Aged; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000276:immunology / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects*; D056747:Immunomodulation; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D012372:ROC Curve; D012751:Sezary Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000077337:Vorinostat
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat