Dataset Information


Correlation of immune phenotype with IDH mutation in diffuse glioma.

ABSTRACT: Background:Tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) are targets of immune checkpoint inhibitors. Methods: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. Results: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). Conclusions: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.


PROVIDER: S-EPMC5737620 | BioStudies | 2017-01-01

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC5373859 | BioStudies
2020-01-01 | S-EPMC7115055 | BioStudies
1000-01-01 | S-EPMC4933482 | BioStudies
2017-01-01 | S-EPMC5432658 | BioStudies
2020-01-01 | S-EPMC7238512 | BioStudies
2019-01-01 | S-EPMC7012245 | BioStudies
2018-01-01 | S-EPMC5835568 | BioStudies
1000-01-01 | S-EPMC4637696 | BioStudies
2014-01-01 | S-EPMC4229642 | BioStudies
1000-01-01 | S-EPMC5379538 | BioStudies