Endothelin B receptor expression in malignant gliomas: the perivascular immune escape mechanism of gliomas.
J Neurooncol
; 127(1): 23-32, 2016 Mar.
Article
en En
| MEDLINE
| ID: mdl-26645886
ABSTRACT
In order to clarify the role of endothelin B receptors (ETBRs) in gliomas, we analyzed cell cultures and surgical specimens of gliomas using RT-PCR and immunohistochemistry. RT-PCR measured the absolute expression of ETBR mRNA in twelve samples, which included gliomas that were classified using the World Health Organization (WHO) classification system Grade I-IV, as well as two glioblastoma cell lines (CCF-STTG1 and U87-MG). Using immunohistochemistry, 77 glioma specimens were evaluated for their expression of ETBR and infiltrating T lymphocytes, including an analysis of cytotoxic T cells (CTLs) and regulatory T lymphocytes (Tregs). The number of ETBR-positive vessels in the glioblastomas (Grade IV) was significantly higher than in other grades of gliomas (comparisons to Grade IV, Grade I p = 0.0323, Grade II p = 0.0009, Grade III p = 0.0273). The ETBR expression rate (defined as the number of ETBR-positive blood vessels divided by the total number of blood vessels) in the glioblastomas was higher than the ETBR expression rate in the low-grade gliomas (compared to Grade IV, Grade I p = 0.0132, Grade II p = 0.0018, Grade III p = 0.0745). In addition, the cases which had an ETBR expression rate of 50 % or higher exhibited fewer infiltrating CTLs and more infiltrating Tregs compared to the cases with an ETBR expression rate <50 % (CTLs p = 0.0342; Tregs p = 0.0175). Isocitrate dehydrogenase 1 (IDH-1) mutations were identified in 21 cases, but there was no correlation between ETBR expression and IDH-1 mutations for any WHO grade. These results suggest that ETBR expression during neo-angiogenesis may interfere with the homing of CTLs around the tumor and be involved in the immune escape mechanism of gliomas.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Encefálicas
/
Linfocitos T Citotóxicos
/
Biomarcadores de Tumor
/
Receptor de Endotelina B
/
Glioma
/
Neovascularización Patológica
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Neurooncol
Año:
2016
Tipo del documento:
Article
País de afiliación:
Japón