Lipid-associated macrophage remodeling is present in the tumor microenvironment after high-grade glioma recurrence.

BACKGROUNDThe inevitable recurrence of most high-grade gliomas (HGG) despite aggressive treatment poses a significant challenge to clinicians. Recently it has been found that exploring the characteristics of cell populations and their biological role in the tumour microenvironment is essential to understand the mechanisms behind tumour recurrence. Focusing on a combination of extensive RNA-seq and single-cell RNA sequencing (scRNA-seq) data, this study explores the mechanisms underlying the process of tumour microenvironment remodelling after HGG recurrence, providing new insights into the recurrence and treatment of HGG.

METHODSClinical information and bulk RNA-Seq data provided by the Chinese Glioma Genome Atlas (CGGA) data and single-cell sequencing data were analysed to compare the differences in the tumour microenvironments in primary and recurrent gliomas using R Seurat and ssGSEA scoring methods. The ssGSEA scores and HGG key clinical features was used to construct a prognostic model by univariate Cox analyses. Differences in clinicopathological characteristics, immune microenvironment, immune checkpoints, with different expressions of lipid-associated macrophages (LAMs) were also investigated. Finally, GO and KEGG were performed on LAMs signature gene annotations to look for possible biological functions and pathways.

RESULTSWe identified a specific macrophage subpopulation defined as lipid-associated macrophages and LAMs cells were significantly increased in patients with HGG recurrence and predicted a poor prognosis. Functionally, LAMs may act as mediators of the immune response, and COX regression analysis revealed that LAMs were found to be an independent prognostic factor for glioma.

CONCLUSIONOur comprehensive analysis suggests that there is a remodelling of LAMs in the tumour microenvironment after HGG recurrence. LAMs could serve as a potential prognostic predictor for patients with glioma, and LAMs could play a role by participating in the immune response and glioma-associated immune checkpoints in order to help maintain the malignant phenotype of the neuroglial tumor cells.