Valproic Acid helps T-Cells Kill Cancer Cells

The antitumour effect of {gamma}{delta} T-cells is enhanced by valproic acid-induced up-regulation of NKG2D ligands

Anticancer Res. 2010 Nov;30(11):4509-13

Suzuki T, Terao S, Acharya B, Naoe M, Yamamoto S, Okamura H, Gotoh A

Abstract

BACKGROUND: The aim of this study wsa to evaluate the additive effect of valproic acid (VPA) to γδ T-cell cytotoxicity against bladder cancer cells.

MATERIALS AND METHODS: Human bladder cancer cell lines TCCSUP and 253J were treated with VPA and mRNA expression of natural killer group 2D (NKG2D) ligands was determined. The antitumour effect of expanded γδ T-cells against zoledronic acid (ZOL) and VPA pre-treated cancer cells was subsequently determined.

RESULTS: VPA increased mRNA expression of NKG2D ligands on both cancer cell types. A blocking study revealed that 253J cells were recognised through NKG2D, while TCCSUP cells were mainly recognised through γδ T-cell receptor. VPA pre-treatment increased sensitivity to cytolysis by γδ T-cells for both cancer cell types, whereas ZOL pre-treatment was only effective against TCCSUP.

CONCLUSION: Induction of NKG2D ligands by VPA increased the susceptibility of cancer cells that are recognised by NKG2D to cytolysis by γδ T-cells.

PMID: 21115900

 

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