title: Endothelin B receptor expression in malignant gliomas: the perivascular immune escape mechanism of gliomas.
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.
authors.affiliation: Department of Pathology, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka, 830-0011, Japan. nakashima_shinji@med.kurume-u.ac.jp.|Department of Neurosurgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan. nakashima_shinji@med.kurume-u.ac.jp.
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakashima
authors.affiliation: Department of Pathology, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sugita
authors.affiliation: Department of Pathology, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Miyoshi
authors.affiliation: Department of Pathology, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Arakawa
authors.affiliation: Department of Pathology, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Muta
authors.affiliation: Department of Pathology, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Yukinao
authors.initials: Y
authors.lastname: Ishibashi
authors.affiliation: Department of Pathology, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Niino
authors.affiliation: Department of Pathology, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka, 830-0011, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
authors.affiliation: Department of Neurosurgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Mizuhiko
authors.initials: M
authors.lastname: Terasaki
authors.affiliation: Department of Neurosurgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Neurosurgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Morioka
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D009154:Mutation / Q000235:genetics; D060787:Neoplasm Grading; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D044023:Receptor, Endothelin B / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D044023:Receptor, Endothelin B; D007521:Isocitrate Dehydrogenase
keywords: Cytotoxic T lymphocyte; Endothelin B receptor; Glioma; Immune escape mechanism