TGF-beta downregulates the activating receptor NKG2D on NK cells and CD8+ T cells in glioma patients

Neuro Oncol. 2010 Jan;12(1):7-13. doi: 10.1093/neuonc/nop009. Epub 2009 Nov 5.

Abstract

The activating receptor NKG2D, expressed by natural killer (NK) cells and CD8(+) T cells, has a role in the specific killing of transformed cells. We examined NKG2D expression in patients with glioblastoma multiforme and found that NKG2D was downregulated on NK cells and CD8(+) T cells. Expression of NKG2D on lymphocytes significantly increased following tumor resection and correlated with an increased ability to kill NKG2D ligand-positive tumor targets. Despite the presence of soluble NKG2D ligands in the sera of glioblastoma patients, NKG2D downregulation was primarily caused by tumor-derived tumor growth factor-beta, suggesting that blocking of this cytokine may have therapeutic benefit.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Brain Neoplasms / immunology
  • Brain Neoplasms / metabolism*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Separation
  • Cytotoxicity, Immunologic / immunology
  • Down-Regulation
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Neoplastic / genetics
  • Glioma / immunology
  • Glioma / metabolism*
  • Humans
  • Immune Tolerance / physiology
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism*
  • NK Cell Lectin-Like Receptor Subfamily K / biosynthesis*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transforming Growth Factor beta / metabolism*

Substances

  • KLRK1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily K
  • Transforming Growth Factor beta