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A disintegrin and metalloproteinases 10 and 17 modulate the immunogenicity of glioblastoma-initiating cells


Wolpert, F; Tritschler, I; Steinle, A; Weller, M; Eisele, G (2014). A disintegrin and metalloproteinases 10 and 17 modulate the immunogenicity of glioblastoma-initiating cells. Neuro-Oncology, 16(3):382-391.

Abstract

BackgroundThere 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.Methods and ResultsHere,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.ConclusionsTherefore, ADAM10 and ADAM17 constitute suitable targets to boost an immune response against GIC.

Abstract

BackgroundThere 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.Methods and ResultsHere,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.ConclusionsTherefore, ADAM10 and ADAM17 constitute suitable targets to boost an immune response against GIC.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2014
Deposited On:06 Jan 2014 13:01
Last Modified:04 Aug 2017 02:17
Publisher:Oxford University Press
ISSN:1522-8517
Additional Information:This is a pre-copyedited, author-produced PDF of an article accepted for publication in Neuro-Oncology following peer review. The definitive publisher-authenticated version Wolpert, F; Tritschler, I; Steinle, A; Weller, M; Eisele, G (2013). A disintegrin and metalloproteinases 10 and 17 modulate the immunogenicity of glioblastoma-initiating cells. Neuro-Oncology. is available online at: http://neuro-oncology.oxfordjournals.org/content/early/2013/12/09/neuonc.not232.long
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/neuonc/not232
PubMed ID:24327582

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