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Molecular Targets for Therapy

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

Leukemia volume 21, pages 2103–2108 (2007)Cite this article

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.

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Acknowledgements

We thank M Yamane, M Mayanagi and Y Ishimaru for their technical assistance. This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, Japan (Tokyo, Japan).

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Authors and Affiliations

  1. Department of Hematology and Oncology, Hokkaido University, Graduate School of Medicine, Sapporo, Japan

    N Kato, J Tanaka, J Sugita, T Toubai, Y Miura, M Ibata, Y Syono & M Imamura

  2. Department of Gastroenterology and Hematology, Hokkaido University, Graduate School of Medicine, Sapporo, Hokkaido, Japan

    S Ota, T Kondo & M Asaka

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  1. N Kato
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Correspondence to J Tanaka.

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Kato, N., Tanaka, J., Sugita, J. et al. 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. Leukemia 21, 2103–2108 (2007). https://doi.org/10.1038/sj.leu.2404862

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