Neuro-Oncology Advance Access published online on November 5, 2009
Neuro-Oncology, doi:10.1093/neuonc/nop009
TGF-β downregulates the activating receptor NKG2D on NK cells and CD8+ T cells in glioma patients
Department of Neurological Surgery, University of California–San Francisco, San Francisco, California (C.A.C., S.J.H., J.J.B., B.J.A., A.T.P.); Department of Microbiology and Immunology and the Cancer Research Institute, University of California–San Francisco, San Francisco, California (L.L.L.)
Corresponding Author: Andrew Parsa, MD, PhD, Department of Neurological Surgery, University of California–San Francisco, 513 Parnassus Avenue, HSW 518, San Francisco, California 94143 (parsaa{at}neurosurg.ucsf.edu).
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Abstract |
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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-β, suggesting that blocking of this cytokine may have therapeutic benefit.
Keywords: GBM, immune escape NKG2D, NK cell, TGF-β
Received April 29, 2009; Accepted June 23, 2009