Transcriptome profile and clinical characterization of ICOS expression in brain gliomas

Abstract

ABSTRACTAimsInducible Co-Stimulator (ICOS), an immune costimulatory molecule, has been found to play an essential role across various malignancies. This study investigated the transcriptome profile and clinical characterization of ICOS in gliomas.MethodsClinical information and transcriptome data of 301 glioma samples were downloaded from the Chinese Glioma Genome Atlas (CGGA) data set for analysis. Furthermore, the results were validated in 697 samples with RNAseq data from the TCGA glioma data set. In addition, single-cell sequencing data from CGGA and GSE 163108 datasets were used to analyze the ICOS expression across different cell types. Statistical analyses and figure production were performed with R-language.ResultsWe found that ICOS was significantly upregulated in higher-grade, IDH wildtype, and mesenchymal subtype of gliomas. Functional enrichment analyses revealed that ICOS was mainly involved in glioma-related immune response. Moreover, ICOS showed a robust correlation with other immune checkpoints, including PD1/PD-L1/PD-L2 pathway, CTLA4, ICOSL (ICOS ligand), and IDO1. Furthermore, based on seven clusters of metagenes, GSVA identified that ICOS was tightly associated with HCK, LCK, MHC-I, MHC-II, STAT1, and interferon, especially with LCK, suggesting a strong correlation between ICOS and T-cell activity in gliomas. In cell lineage analysis, ICOS-higher gliomas tended to recruit dendritic cells, monocytes, and macrophages into the tumor microenvironment. Single-cell sequencing analysis indicated that ICOS was highly expressed by regulatory T cells (Treg). Finally, patients with higher ICOS had shortened survival. ICOS was an independent prognosticator for glioma patients.ConclusionsHigher ICOS was correlated with more malignancy of gliomas and significantly associated with Treg activity among glioma-related immune responses. Moreover, ICOS could contribute as an independent prognostic factor for gliomas. Our study highlighted the role of ICOS in glioma and may facilitate therapeutic strategies targeting ICOS for glioma.