A possible mechanism of impaired NK cytotoxicity in cancer patients: Down-regulation of DAP10 by TGF-β1

June Chul Lee, Kyung Mi Lee, Yong Oon Ahn, Beomseok Suh, Dae Seog Heo

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11 Citations (Scopus)

Abstract

Aims and background. Elevated TGF-β1 secretion and down-modulation of NKG2D underlies impaired NK cytotoxicity in cancer patients. However, the molecular mechanism of immunosuppression by TGF-β1 is not yet clarified. Methods. IL-2-activated human NK cells were cultured with TGF-β1. Protein levels of NKG2D and DAP10 were examined by FACS or immunoblot analyses. Real-time RTPCR was performed to quantify the transcription levels. MAPK inhibitors were used to investigate intracellular signaling. Results. TGF-β1 down-regulated total and surface NKG2D, which was partially dependent on transcriptional regulation. TGF-β1 treatment of human NK cells resulted in significant changes in both transcriptional and translational levels of DAP10. Moreover, treatment with bafilomycin A1 or folimycin restored total NKG2D levels in TGF-β1-treated NK cells. The impaired NKG2D down-modulation by TGF-β1 was not associated with activation of the MAPK signaling pathway. Conclusions. TGF-β1 down-modulates surface NKG2D expression by controlling the transcriptional and translational levels of DAP10.

Original languageEnglish
Pages (from-to)350-357
Number of pages8
JournalTumori
Volume97
Issue number3
Publication statusPublished - 2011 May 1

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Keywords

  • DAP10
  • Human NK cells
  • NKG2D
  • TGF-β
  • Tumor immunity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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