TGF-beta downregulates the activating receptor NKG2D on NK cells and CD8+ T cells in glioma patients.
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.
Department of Neurological Surgery, University of California-San Francisco, San Francisco, California 94143, USA.
Courtney A
CA
Crane
Seunggu J
SJ
Han
Jeffery J
JJ
Barry
Brian J
BJ
Ahn
Lewis L
LL
Lanier
Andrew T
AT
Parsa
D001932:Brain Neoplasms / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005910:Glioma / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016212:Transforming Growth Factor beta