Related Experiment Video
Updated: Mar 2, 2026
A Protocol for Explant Cultures of IDH1-mutant Diffuse Low-grade Gliomas
Published on: May 9, 2025
Correlation of immune phenotype with IDH mutation in diffuse glioma
Anna Sophie Berghoff1, Barbara Kiesel1, Georg Widhalm1
1Institute of Neurology, Medical University of Vienna, Vienna, Austria; Department of Medicine I, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Neurosurgery, Medical University of Vienna, Vienna, Austria; Department of Genome Science, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia; Laboratory of Brain Tumor Biology and Genetics, Service of Neurosurgery & Neuroscience Research Center, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
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.
