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Front. Immunol. | doi: 10.3389/fimmu.2018.00617

Decitabine inhibits gamma delta T cell cytotoxicity by promoting KIR2DL2/3 expression

 Chao Niu1, Min Li1,  Shan Zhu1, Yongchong Chen1, Lei Zhou1, Dongsheng Xu1, Wei Li1, Jiuwei Cui1*, Yongjun Liu1* and  Jingtao Chen1*
  • 1First Hospital, Jilin University, China

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 methyltransferase inhibitor, Adoptive cell immunotherapy, DNA Methylation, Killer Ig-like receptors, myelodysplastic syndrome

Received: 31 Oct 2017; Accepted: 12 Mar 2018.

Edited by:

Anahid Jewett, University of California, Los Angeles, United States

Reviewed by:

Kerry S. Campbell, Fox Chase Cancer Center, United States
Zong Sheng Guo, Harvard University, United States  

Copyright: © 2018 Niu, Li, Zhu, Chen, Zhou, Xu, Li, Cui, Liu and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Jiuwei Cui, First Hospital, Jilin University, Changchun, China,
Prof. Yongjun Liu, First Hospital, Jilin University, Changchun, China,
Prof. Jingtao Chen, First Hospital, Jilin University, Changchun, China,