%0 Generic %A Mu, Luyan %A Long, Yu %A Yang, Changlin %A Jin, Linchun %A Tao, Haipeng %A Ge, Haitao %A Chang, Yifan E. %A Karachi, Aida %A Kubilis, Paul S. %A De Leon, Gabriel %A Qi, Jiping %A J. Sayour, Elias %A A. Mitchell, Duane %A Lin, Zhiguo %A Huang, Jianping %D 2018 %T Table1.PDF %U https://frontiersin.figshare.com/articles/dataset/Table1_PDF/6045647 %R 10.3389/fnmol.2018.00082.s006 %2 https://frontiersin.figshare.com/ndownloader/files/10884236 %K gliomas %K immune checkpoint %K PD-L1 %K DNA methylation %K IDH mutation %K 2-hydroxyglutarate %X

Background: Malignant gliomas are heterogeneous brain tumors with the potential for aggressive disease progression, as influenced by suppressive immunoediting. Given the success and enhanced potential of immune-checkpoint inhibitors in immunotherapy, we focused on the connections between genetic alterations affected by IDH1 mutations and immunological landscape changes and PDL-1 expression in gliomas.

Methods: Paired surgically resected tumors from lower-grade gliomas (LGGs) and glioblastomas (GBM) were investigated, and a genetic analysis of patients' primary tumor samples culled from TCGA datasets was performed.

Results: The results demonstrate that when compared with IDH1-mutant tumors, IDH1 wildtype tumors represent an immunosuppression landscape and elevated levels of PD-L1 expression. DNA hypo-methylation of the PD-L1 gene, as well as high gene and protein expressions, were observed in the wildtype tumors. We also found that quantitative levels of IDH1 mutant proteins were positively associated with recurrence-free survival (RFS). A key product of the IDH1 mutation (2-hydroxyglutarate) was found to transiently increase DNA methylation and suppress PD-L1 expression.

Conclusions: IDH1 mutations impact the immune landscape of gliomas by affecting immune infiltrations and manipulating checkpoint ligand PD-L1 expression. Applications of immune checkpoint inhibitors may be beneficial for chemoradiation-insensitive IDH1-wildtype gliomas.

%I Frontiers