RRC ID 68533
Author Kato N, Tanaka J, Sugita J, Toubai T, Miura Y, Ibata M, Syono Y, Ota S, Kondo T, Asaka M, Imamura M.
Title Regulation of the expression of MHC class I-related chain A, B (MICA, MICB) via chromatin remodeling and its impact on the susceptibility of leukemic cells to the cytotoxicity of NKG2D-expressing cells.
Journal Leukemia
Abstract Innate immune cells such as natural killer (NK) cells play a crucial role in antitumor immune responses. NKG2D is a major activating immunoreceptor expressed in not only NK cells but also CD8+ T cells and shows cytotoxicity against tumors by recognizing its ligands major histocompatibility complex class I-related chain A and B (MICA and MICB) on tumor cells. Recently, it has been suggested that NKG2D-mediated cytotoxicity correlates with the expression levels of NKG2D ligands on target cells. In this study, we were able to increase the expression levels of MICA and MICB on leukemic cell lines and patients' leukemic cells by treatment with trichostatin A (TsA), a histone deacetylase (HDAC) inhibitor. Chromatin immunoprecipitation (ChIP) assays revealed that treatment with TsA resulted in increased acetylation of histone H3 and decreased association with HDAC1 at the promoters of MICA and MICB. Intriguingly, upregulation of MICA and MICB by treatment with TsA led to enhancement of the susceptibility of leukemic cells to the cytotoxicity of NKG2D-expressing cells. Our results suggest that regulation of the expression of NKG2D ligands by treatment with chromatin-remodeling drugs may be an attractive strategy for immunotherapy.
Volume 21(10)
Pages 2103-8
Published 2007-10-1
DOI 10.1038/sj.leu.2404862
PII 2404862
PMID 17625602
MeSH Adult Aged Cell Line, Tumor Chromatin Assembly and Disassembly Female Gene Expression Regulation, Leukemic* Genes, MHC Class I* Genetic Predisposition to Disease* Histocompatibility Antigens Class I / biosynthesis* Histocompatibility Antigens Class I / metabolism Histones / metabolism Humans Hydroxamic Acids / pharmacology Jurkat Cells K562 Cells Male Middle Aged NK Cell Lectin-Like Receptor Subfamily K Protein Synthesis Inhibitors / pharmacology Receptors, Immunologic / metabolism Receptors, Natural Killer Cell
IF 8.665
Human and Animal Cells BALL-1(RCB0256) Jurkat(RCB0806) K562(RCB0027)