In:
Neuropathology and Applied Neurobiology, Wiley, Vol. 41, No. 2 ( 2015-02)
Abstract:
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, TNFRSF 9 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 TNFRSF 9 in human gliomas. Methods We investigated TNFRSF 9 expression in normal human central nervous system ( CNS ) tissue and glioma specimens using immunohistochemistry, immunofluorescence and W estern blotting techniques. Results Our results show that TNFRSF 9 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 TNFRSF 9 in mainly non‐neoplastic reactive astrocytes and excludes classic immunological cell types, namely lymphocytes and microglia as the source of TNFRSF 9. Moreover, TNFRSF 9 is predominantly expressed in a perivascular and peritumoural distribution with significantly higher expression in IDH ‐1 mutant gliomas. Conclusions Our findings provide a novel, TNFRSF 9‐positive, reactive astrocytic phenotype and challenge the therapeutic suitability of TNFRSF 9 as a promising target for human gliomas.
Type of Medium:
Online Resource
ISSN:
0305-1846
,
1365-2990
DOI:
10.1111/nan.2015.41.issue-2
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2008293-9