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>