Epithelial-mesenchymal transition is the main way in which glioma-associated microglia/macrophages promote glioma progression

Abstract

Microglia/macrophages make up the largest population of tumor-infiltrating cells. Numerous studies have demonstrated that glioma-associated microglia/macrophages (GAMs) could promote the malignant progression of gliomas in various pathways. However, the primary function of GAMs in glioma remains inconclusive. First, by the CIBERSORT algorithm, we evaluated the content of microglia/macrophages in glioma tissues by bioinformatic analysis of omic data from thousands of glioma samples. Subsequently, we analyzed and confirmed the significant relationship between GAMs and the malignant phenotype of glioma, including survival time, IDH mutation status, and time of symptom onset. Afterward, Epithelial-Mesenchymal Transition (EMT) was identified by Gene Set Enrichment Analysis (GSEA) from numerous biological processes as the most relevant mechanism of malignant progression to GAMs. Moreover, a series of clinical samples were detected, including normal brain and various-grade glioma tissues. The results not only showed that GAMs were significantly associated with gliomas and their malignancy but also that GAMs were highly correlated with the degree of EMT in gliomas. In addition, we isolated GAMs from glioma samples and constructed co-culture models (in vitro) to demonstrate the promotion of the EMT process in glioma cells by GAMs. In conclusion, our study clarified that GAMs exert oncogenic effects with EMT in gliomas, suggesting the possibility of GAMs as immunotherapeutic targets.

Keywords: epithelial-mesenchymal transition; glioma; glioma progression; glioma-associated microglia/macrophages; tumor microenvironment.