10.3389/fnmol.2018.00082.s005 Luyan Mu Luyan Mu Yu Long Yu Long Changlin Yang Changlin Yang Linchun Jin Linchun Jin Haipeng Tao Haipeng Tao Haitao Ge Haitao Ge Yifan E. Chang Yifan E. Chang Aida Karachi Aida Karachi Paul S. Kubilis Paul S. Kubilis Gabriel De Leon Gabriel De Leon Jiping Qi Jiping Qi Elias J. Sayour Elias J. Sayour Duane A. Mitchell Duane A. Mitchell Zhiguo Lin Zhiguo Lin Jianping Huang Jianping Huang Presentation1.pdf Frontiers 2018 gliomas immune checkpoint PD-L1 DNA methylation IDH mutation 2-hydroxyglutarate 2018-03-28 04:21:05 Presentation https://frontiersin.figshare.com/articles/presentation/Presentation1_pdf/6045644 <p>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.</p><p>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.</p><p>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.</p><p>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.</p>