Open AccessAtaxia–telangiectasia mutated kinase‐mediated upregulation of NKG 2 D ligands on leukemia cells by resveratrol results in enhanced natural killer cell susceptibility
Author(s) -
Luis Espinoza J.,
Takami Akiyoshi,
Trung Ly Q.,
Nakao Shinji
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12141
Subject(s) - nkg2d , resveratrol , cytotoxic t cell , downregulation and upregulation , natural killer cell , cancer research , biology , chemistry , microbiology and biotechnology , biochemistry , in vitro , gene
The powerful activating receptor NKG 2 D is expressed by natural killer ( NK ) cells and promotes cytotoxic lysis of cancer cells expressing NKG2D ligands (NKG2D‐Ls). We report the effective induction of NKG 2 D ‐ L s, achieved with the naturally occurring polyphenol resveratrol, in a broad range of leukemia cells. In this study, resveratrol upregulated the NKG 2 D ‐ L s MHC class I chain‐related proteins MICA and MICB , and UL 16‐binding proteins ULBP 1, ULBP 2, and ULBP 3 in most of the leukemia cells analyzed. Ligand upregulation induced by resveratrol was impaired by pharmacological and genetic disruption of ataxia–telangiectasia mutated kinase, the main regulator of NKG 2 D ‐ L expression. Leukemia cells treated with resveratrol were more susceptible to killing by NK cells than untreated cells, and the enhanced cytotoxicity of NK cells was blocked by treatment of NK cells with anti‐ NKG 2 D m A bs. Interestingly, resveratrol consistently upregulated the NKG 2 D receptor expression and enhanced NKG 2 D ‐mediated functions in resting NK cells obtained from healthy individuals. Therefore, resveratrol has attractive immunotherapeutic potential.