Exposure to a histone deacetylase inhibitor has detrimental effects on human lymphocyte viability and function

• Published in: Cancer immunology research 2014-05, Vol.2 (5), p.459-468
• Main Authors: Wong, Deborah J L, Rao, Amol, Avramis, Earl, Matsunaga, Douglas R, Komatsubara, Kimberly M, Atefi, Mohammad S, Escuin-Ordinas, Helena, Chodon, Thinle, Koya, Richard C, Ribas, Antoni, Comin-Anduix, Begoña
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Cell Cycle - drug effects; Cell Line, Tumor; Cell Survival - drug effects; DNA Damage - drug effects; Histone Deacetylase Inhibitors - pharmacology; Humans; Hydroxamic Acids - pharmacology; Indoles - pharmacology; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Lymphocytes - drug effects; Lymphocytes - immunology; Phosphoproteins - metabolism; Proteome; Single-Cell Analysis
• ISSN: 2326-6066; 2326-6074
• DOI: 10.1158/2326-6066.CIR-13-0188

Histone deacetylase inhibitors (HDACi) have been reported to increase tumor antigen expression, and have been successfully tested as adjuvants for melanoma immunotherapy in mouse models. In this work, we tested the effects of a pan-HDACi on human lymphocytes and melanoma cell lines. Effects of the pan-HDACi panobinostat (LBH589) on cell viability, cell cycle, apoptosis, and DNA damage were determined in peripheral blood mononuclear cells (PBMC) from 2 healthy donors, 13 patients with metastatic melanoma, 2 bone marrow samples from patients with different malignances, and 12 human melanoma cell lines. Intracellular signaling in lymphocytes, with or without cytokine stimulation, was analyzed by phospho-flow cytometry in one of each type. The IC50 in PBMCs was 600 nmol/L in melanoma cell lines; >40% apoptotic cell death in PBMCs versus