AUTHOR=Luo Wei , Quan Qi , Jiang Jiaxin , Peng Roujun 

TITLE=An immune and epithelial–mesenchymal transition-related risk model and immunotherapy strategy for grade II and III gliomas

JOURNAL=Frontiers in Genetics

VOLUME=Volume 13 - 2022

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.1070630

DOI=10.3389/fgene.2022.1070630

ISSN=1664-8021

ABSTRACT=Grade II and III gliomas were heterogeneous and aggressive disease. More efficient prognosis model and treatment methods are needed. This study aims to construct a new risk model and propose a new strategy for grade II and III gliomas. The data was downloaded from The Cancer Genome Atlas (TCGA), The Gene Expression Omnibus (GEO), Gene set enrichment analysis (GSEA) and EMTome website for analysis. Human Cell Landscape website and Genomics of Drug Sensitivity in Cancer website were used for single cell analysis and drug susceptibility analysis. Gene set enrichment analysis, Gene function enrichment analysis, Univariate and multivariate Cox regression analysis, Pearson’s correlation analysis, Log-rank test, Kaplan-Meier survival analysis and ROC analysis were performed. We constructed an immune-related prognostic model associated with isocitrate dehydrogenase 1 (IDH1) mutation status. By analyzing the immune microenvironment of patients with different risk scores, we found that high-risk patients were more likely to have an inflammatory immune microenvironment and higher programmed death-ligand 1 (PD-L1) expression level. Epithelial mesenchymal transition (EMT) related gene sets were significantly enriched in the high-risk group, and EMT phenotype was associated with a decrease in CD8+ T cells and an increase in M2 macrophages. Transforming growth factor-β (TGF-β) signaling was the most important signaling in inducing EMT, and TGFB1/TGFBR1 was correlated with CD8+ T cytopenia and M2 macrophage increase. Survival analysis showed that simultaneous low expression of TGFBR1 and PD-L1 has better survival results. Through single-cell analysis, we found that TGFB1 is closely related to microglia and macrophages especially M2 macrophages. Finally, we discussed the sensitivity of TGFB1 inhibitors in gliomas using cell line susceptibility data. These results demonstrated a potential immunotherapy strategy in combination with TGFB1/TGFBR1 inhibitor and PD-1/PD-L1 inhibitor for grade II and III gliomas.