CD44-Mediated Poor Prognosis in Glioma Is Associated With M2-Polarization of Tumor-Associated Macrophages and Immunosuppression.

BACKGROUND

Glioma is the most common primary brain tumor with a poor prognosis. Key genes that are negatively related to prognosis may provide the therapy targets to cure glioma. To clarify the role of in glioma, we explored its function at bulk-transcriptome, spatial and single-cell transcriptome levels.

METHODS

In total, expression profiles with survival data of whole-grade glioma from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), RNA-seq data with anatomic information of glioblastoma (GBM) from the Ivy Glioblastoma Atlas Project, RNA-sequencing (RNA-seq) data from recurrent GBM receiving adjuvant anti immunotherapy accessed through GSE121810, and single-cell RNA-seq data of GBM under accession GSE103224 were enrolled in this study. -specific findings were further analyzed by R language.

RESULTS

is positively correlated with WHO grade of malignancy and is negatively related to prognosis in glioma. Meanwhile, predominantly expresses in GBM mesenchymal subtype, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses reveal that positively coexpressed genes are closely related to glioma immunity. Moreover, + cells mainly distribute in perinecrotic region with high expression of immune factors. At single-cell resolution, only malignant tumor cells, tumor-associated macrophages (TAMs), and T cells express in GBM. + malignant tumor cells are in mesenchymal-1-like (MES1-like) cellular state, and + TAMs are in M2 phenotype. + T cells have high expression of both and . and its directly interacted inhibitory immunomodulators are upregulated in patients with nonresponder recurrent GBM treated with blockade therapy.

CONCLUSION

Our work demonstrates that , a new M2 TAM biomarker, is involved in immune suppressor and promote glioma progression in glioma microenvironment. These results expand our understanding of -specific clinical and immune features in glioma.