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Inhibition of cell‐mediated immunity by the histone deacetylase inhibitor vorinostat: Implications for therapy of cutaneous T‐cell lymphoma
Author(s) -
Stephen Sasha,
Morrissey Kelly A.,
Benoit Bernice M.,
Kim Ellen J.,
Vittorio Carmela C.,
Nasta Sunita D.,
Showe Louise C.,
Wysocka Maria,
Rook Alain H.
Publication year - 2012
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.22231
Subject(s) - vorinostat , histone deacetylase inhibitor , histone deacetylase , cutaneous t cell lymphoma , immune system , immunology , medicine , lymphoma , immunosuppression , t cell , cancer research , immunotherapy , immunity , population , pharmacology , biology , histone , mycosis fungoides , gene , biochemistry , environmental health
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.