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Tumour necrosis factor receptor superfamily member 9 (TNFRSF9) is up-regulated in reactive astrocytes in human gliomas

Aims The prognosis of patients with malignant gliomas is still dismal despite maximum treatment. Novel therapeutic alternatives targeting tumorigenic pathways are, therefore, demanded. In murine glioma models, targeting of tumour necrosis factor receptor superfamily (TNFRSF) 9 led to complete tumour...

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Main Authors: Blank, Anna-Eva (Author) , Baumgarten, Peter (Author) , Zeiner, Pia (Author) , Zachskorn, Cornelia (Author) , Löffler, Christian (Author) , Schittenhelm, Jens (Author) , Czupalla, Cathrin J. (Author) , Capper, David (Author) , Plate, Karl H. (Author) , Harter, Patrick N. (Author) , Mittelbronn, Michel (Author)
Format: Article (Journal)
Language:English
Published: 2015
In: Neuropathology & applied neurobiology
Year: 2014, Volume: 41, Issue: 2, Pages: e56-e67
ISSN:1365-2990
DOI:10.1111/nan.12135
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1111/nan.12135
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/nan.12135
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Author Notes:Anna-Eva Blank, Peter Baumgarten, Pia Zeiner, Cornelia Zachskorn, Christian Löffler, Jens Schittenhelm, Cathrin J. Czupalla, David Capper, Karl H. Plate, Patrick N. Harter and Michel Mittelbronn
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Summary:Aims The prognosis of patients with malignant gliomas is still dismal despite maximum treatment. Novel therapeutic alternatives targeting tumorigenic pathways are, therefore, demanded. In murine glioma models, targeting of tumour necrosis factor receptor superfamily (TNFRSF) 9 led to complete tumour eradication. Thus, TNFRSF9 might also constitute a promising target in human diffuse gliomas. As there is a lack of data, we aimed to define the expression pattern and cellular source of TNFRSF9 in human gliomas. Methods We investigated TNFRSF9 expression in normal human central nervous system (CNS) tissue and glioma specimens using immunohistochemistry, immunofluorescence and Western blotting techniques. Results Our results show that TNFRSF9 is considerably up-regulated in human gliomas when compared with normal brain tissue. In addition, our data provides evidence for an immune cell-independent de novo expression pattern of TNFRSF9 in mainly non-neoplastic reactive astrocytes and excludes classic immunological cell types, namely lymphocytes and microglia as the source of TNFRSF9. Moreover, TNFRSF9 is predominantly expressed in a perivascular and peritumoural distribution with significantly higher expression in IDH-1 mutant gliomas. Conclusions Our findings provide a novel, TNFRSF9-positive, reactive astrocytic phenotype and challenge the therapeutic suitability of TNFRSF9 as a promising target for human gliomas.
Item Description:Published online Article Accepted on 10 March 2014
Gesehen am 26.05.2020
Physical Description:Online Resource
ISSN:1365-2990
DOI:10.1111/nan.12135

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