title: A disintegrin and metalloproteinases 10 and 17 modulate the immunogenicity of glioblastoma-initiating cells.
abstract: BACKGROUND
  There are emerging reports that the family of a disintegrin and metalloproteinases (ADAM) are involved in the maintenance of the malignant phenotype of glioblastomas. Notably, ADAM proteases 10 and 17 might impair the immune recognition of glioma cells via the activating immunoreceptor NKG2D by cleavage of its ligands from the cell surface. Glioblastoma-initiating cells (GIC) with stem cell properties have been identified as an attractive target for immunotherapy. However, GIC immunogenicity seems to be low.
  
  
  RESULTS
  Here,we show that ADAM10 and ADAM17 are expressed on the cell surface of GIC and contribute to an immunosuppressive phenotype by cleavage of ULBP2. The cell surface expression of ULBP2 is enhanced upon blocking ADAM10 and ADAM17, and treatment with ADAM10 and ADAM17specific inhibitors leads to enhanced immunerecognition of GIC by natural killer cells.
  
  
  CONCLUSIONS
  Therefore, ADAM10 and ADAM17 constitute suitable targets to boost an immune response against GIC.
authors: Department of Neurology, University Hospital Zurich, Zurich, Switzerland (F.W., I.T., M.W., G.E.); Institute for Molecular Medicine, Goethe University Frankfurt am Main, Frankfurt am Main, Germany (A.S.).
authors: Fabian
authors: F
authors: Wolpert
authors: Isabel
authors: I
authors: Tritschler
authors: Alexander
authors: A
authors: Steinle
authors: Michael
authors: M
authors: Weller
authors: Günter
authors: G
authors: Eisele
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000072197:ADAM10 Protein; D000072198:ADAM17 Protein; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001932:Brain Neoplasms / Q000276:immunology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004151:Dipeptides / Q000494:pharmacology; D058851:GPI-Linked Proteins / Q000378:metabolism; D005909:Glioblastoma / Q000276:immunology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000276:immunology*; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors
chemical_list: C555398:3-(formylhydroxyamino)-2-(3-phenyl-1-propyl)butanoic acid (2,2-dimethyl-1-methylcarbamoyl-1-propyl)amide; D004151:Dipeptides; D058851:GPI-Linked Proteins; C492546:GW280264X; D006877:Hydroxamic Acids; D036341:Intercellular Signaling Peptides and Proteins; C527085:KLRK1 protein, human; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D018125:Receptors, Transforming Growth Factor beta; C423230:ULBP2 protein, human; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human
keywords: NK cell; NKG2D; a disintegrin and metalloproteinase (ADAM); glioblastoma; immunotherapy; stem cell