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Front Immunol. 2018 Mar 26;9:617. doi: 10.3389/fimmu.2018.00617. eCollection 2018.

Decitabine Inhibits Gamma Delta T Cell Cytotoxicity by Promoting KIR2DL2/3 Expression.

Author information

1
Department of Translational Medicine, The First Hospital of Jilin University, Changchun, China.
2
Department of Cancer Center, The First Hospital of Jilin University, Changchun, China.
3
Sanofi Research and Development, Cambridge, MA, United States.

Abstract

Gamma delta (γδ) T cells, which possess potent cytotoxicity against a wide range of cancer cells, have become a potential avenue for adoptive immunotherapy. Decitabine (DAC) has been reported to enhance the immunogenicity of tumor cells, thereby reinstating endogenous immune recognition and tumor lysis. However, DAC has also been demonstrated to have direct effects on immune cells. In this study, we report that DAC inhibits γδ T cell proliferation. In addition, DAC increases the number of KIR2DL2/3-positive γδ T cells, which are less cytotoxic than the KIR2DL2/3-negative γδ T cells. We found that DAC upregulated KIR2DL2/3 expression in KIR2DL2/3-negative γδ T cells by inhibiting KIR2DL2/3 promoter methylation, which enhances the binding of KIR2DL2/3 promoter to Sp-1 and activates KIR2DL2/3 gene expression. Our data demonstrated that DAC can inhibit the function of human γδ T cells at both cellular and molecular levels, which confirms and extrapolates the results of previous studies showing that DAC can negatively regulate the function of NK cells and αβ T cells of the immune system.

KEYWORDS:

DNA methylation; DNA methyltransferase inhibitor; adoptive cell immunotherapy; killer Ig-like receptors; myelodysplastic syndrome

PMID:
29632540
PMCID:
PMC5879086
DOI:
10.3389/fimmu.2018.00617
[Indexed for MEDLINE]
Free PMC Article

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