Correlation of immune phenotype with IDH mutation in diffuse glioma.
Détails
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Etat: Public
Version: Author's accepted manuscript
Etat: Public
Version: Author's accepted manuscript
ID Serval
serval:BIB_E5DE312C831C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Correlation of immune phenotype with IDH mutation in diffuse glioma.
Périodique
Neuro-oncology
ISSN
1523-5866 (Electronic)
ISSN-L
1522-8517
Statut éditorial
Publié
Date de publication
19/10/2017
Peer-reviewed
Oui
Volume
19
Numéro
11
Pages
1460-1468
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
Tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) are targets of immune checkpoint inhibitors.
Forty-three World Health Organization (WHO) grade II/III gliomas (39 IDH-mutant [mut], 4 IDH-wildtype [wt]) and 14 IDH-mut glioblastomas (GBM) were analyzed for TIL (CD3+; PD1+) infiltration and PD-L1 expression. Results were compared with the data of a previously published series of 117 IDH-wt glioblastomas. PD-L1 gene expression levels were evaluated in 677 diffuse gliomas grades II-IV from The Cancer Genome Atlas (TCGA) database.
TIL and PD-L1 expression were observed in approximately half of WHO grade II/III gliomas. IDH-wt status was associated with significantly higher TIL infiltration and PD-L1 expression among all (grades II-IV) cases (n = 174, P < 0.001) and within the cohort of glioblastomas (n = 131, P < 0.001). In low-grade glioma (LGG) and glioblastoma cohorts of TCGA, significantly higher PD-L1 gene expression levels were evident in IDH-wt compared with IDH-mut samples (LGG: N = 516; P = 1.933e-11, GBM: N = 161; P < 0.009). Lower PD-L1 gene expression was associated with increased promoter methylation (Spearman correlation coefficient -0.36; P < 0.01) in the LGG cohort of TCGA. IDH-mut gliomas had higher PD-L1 gene promoter methylation levels than IDH-wt gliomas (P < 0.01).
The immunological tumor microenvironment of diffuse gliomas differs in association with IDH mutation status. IDH-wt gliomas display a more prominent TIL infiltration and higher PD-L1 expression than IDH-mut cases. Mechanistically this may be at least in part due to differential PD-L1 gene promoter methylation levels. Our findings may be relevant for immune modulatory treatment strategies in glioma patients.
Forty-three World Health Organization (WHO) grade II/III gliomas (39 IDH-mutant [mut], 4 IDH-wildtype [wt]) and 14 IDH-mut glioblastomas (GBM) were analyzed for TIL (CD3+; PD1+) infiltration and PD-L1 expression. Results were compared with the data of a previously published series of 117 IDH-wt glioblastomas. PD-L1 gene expression levels were evaluated in 677 diffuse gliomas grades II-IV from The Cancer Genome Atlas (TCGA) database.
TIL and PD-L1 expression were observed in approximately half of WHO grade II/III gliomas. IDH-wt status was associated with significantly higher TIL infiltration and PD-L1 expression among all (grades II-IV) cases (n = 174, P < 0.001) and within the cohort of glioblastomas (n = 131, P < 0.001). In low-grade glioma (LGG) and glioblastoma cohorts of TCGA, significantly higher PD-L1 gene expression levels were evident in IDH-wt compared with IDH-mut samples (LGG: N = 516; P = 1.933e-11, GBM: N = 161; P < 0.009). Lower PD-L1 gene expression was associated with increased promoter methylation (Spearman correlation coefficient -0.36; P < 0.01) in the LGG cohort of TCGA. IDH-mut gliomas had higher PD-L1 gene promoter methylation levels than IDH-wt gliomas (P < 0.01).
The immunological tumor microenvironment of diffuse gliomas differs in association with IDH mutation status. IDH-wt gliomas display a more prominent TIL infiltration and higher PD-L1 expression than IDH-mut cases. Mechanistically this may be at least in part due to differential PD-L1 gene promoter methylation levels. Our findings may be relevant for immune modulatory treatment strategies in glioma patients.
Mots-clé
Adult, Aged, B7-H1 Antigen/genetics, B7-H1 Antigen/metabolism, Biomarkers, Tumor/genetics, Biomarkers, Tumor/metabolism, Brain Neoplasms/genetics, Brain Neoplasms/immunology, Brain Neoplasms/metabolism, Brain Neoplasms/pathology, Cohort Studies, Female, Follow-Up Studies, Glioma/genetics, Glioma/immunology, Glioma/metabolism, Glioma/pathology, Humans, Isocitrate Dehydrogenase/genetics, Lymphocytes, Tumor-Infiltrating/immunology, Lymphocytes, Tumor-Infiltrating/metabolism, Male, Middle Aged, Mutation, Phenotype, Prognosis, Promoter Regions, Genetic, IDH mutation, PD-L1, glioblastoma, immune microenvironment, low grade glioma, promoter methylation
Pubmed
Web of science
Open Access
Oui
Création de la notice
30/05/2017 17:19
Dernière modification de la notice
20/08/2019 17:09