AUTHOR=Luo Cong , Liu Zhixiong , Ye Wenrui , Liu Fangkun 

TITLE=Immune Infiltration-Related Signature Predicts Risk Stratification and Immunotherapy Efficacy in Grade II and III Gliomas

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.756005

DOI=10.3389/fcell.2021.756005

ISSN=2296-634X

ABSTRACT=<p><bold>Background:</bold> Tumor microenvironment, especially infiltrating immune cell, is crucial for solid tumors including glioma. However, the hub genes as well as their effects on patient prognosis and immunotherapy efficacy remain obscure.</p><p><bold>Methods:</bold> We employed a total of 952 lower grade glioma (LGG) patients from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases, and 24 samples in our hospital for subsequent analyses. Abundances of immune infiltrates were evaluated using CIBERSORT and ImmuCellAI. Their correlations with prognosis were assessed by log-rank test. Immune infiltration-related hub genes were obtained from overlapped differential expressed genes (DEGs) in various subsets of survival-related immune cell types. The risk signature was constructed by Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis. The functional analyses were estimated by GVSA and Gene Set Enrichment Analysis (GSEA) algorithms. And protein–protein interaction enrichment analysis was carried out with the Metascape database integrating STRING, BioGrid, OmniPath, and InWeb_IM.</p><p><bold>Results:</bold> Among the 21 infiltrates, the abundances of five immune infiltrates were correlated with overall survival (OS) in LGG patients. Higher abundances of naïve CD4+ T cells (<italic>p</italic> = 0.002), activated mast cells (<italic>p</italic> = 0.015), and monocytes (<italic>p</italic> = 0.014) were correlated with better prognosis, while higher abundances of resting memory CD4+ T cells (<italic>p</italic> = 0.015) and M1 macrophages (<italic>p</italic> = 0.020) correlated with poorer OS. We finally obtained 44 hub genes and constructed an immune infiltration-related signature (IIRS). The IIRS correlates with clinicopathological characteristics and exhibited potential power in predicting the immunotherapy efficacy. The IRRS correlates with cancer related pathways, especially “epithelial-mesenchymal transition (EMT),” and cytotoxic T lymphocytes.</p><p><bold>Conclusion:</bold> Our study constructed and validated a novel signature for risk stratification and prediction of immunotherapy response in grade II and III gliomas, which was closely associated with glioma immune microenvironment and could serve as a promising prognostic biomarker for glioma patients.</p>