title: Rescue of major histocompatibility-DR surface expression in retinoblastoma-defective, non-small cell lung carcinoma cells by the MS-275 histone deacetylase inhibitor.
abstract: Major histocompatibility (MHC) class II expression is ordinarily inducible by interferon-gamma (IFN-gamma), but the induction is repressed in retinoblastoma protein (Rb)-defective cells. The repression can be rescued by histone deacetylase (HDAC) inhibitor treatment, but this has never been shown for an HDAC inhibitor that is suitable for clinical trials and eventual patient therapy. Here we demonstrate that the HDAC inhibitor, MS-275, can rescue the IFN-gamma inducibility of human leukocyte antigen (HLA)-DR in non-small cell lung cancer cells. This HDAC inhibitor is currently being tested in phase I/II clinical trials for non-small cell lung cancer. We further verified that the MS-275 effect is related to an HDAC tethered to the HLA-DRA promoter by the transcription factor, YY1. HDAC inhibitors that can be used to treat patients may augment the expression of tumor cell MHC class II, and the results suggest an opportunity to determine the immunological consequences of HDAC inhibitor treatment in tumor therapy.
authors.affiliation: Department of Molecular Medicine, College of Medicine, University of South Florida, Florida 33612, USA.
authors.forename: Melissa Ihla
authors.initials: MI
authors.lastname: Niesen
authors.forename: George
authors.initials: G
authors.lastname: Blanck
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung; D045744:Cell Line, Tumor; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D008175:Lung Neoplasms; D011725:Pyridines / Q000494:pharmacology*; D016160:Retinoblastoma Protein / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D006684:HLA-DR Antigens; D056572:Histone Deacetylase Inhibitors; D011725:Pyridines; D016160:Retinoblastoma Protein; C118739:entinostat