Abstract
The glioblastoma microenvironment predominantly contains tumor-associated macrophages that support tumor growth and invasion. We investigated the relationship between tumor radiosensitivity and infiltrating M1/M2 macrophage profiles in public datasets of primary and recurrent glioblastoma. We estimated the radiosensitivity index (RSI) score based on gene expression rankings. Macrophages were profiled using the deconvolution algorithm CIBERSORTx. Samples from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), the Ivy Glioblastoma Atlas Project dataset, a single-cell RNA sequencing dataset (GSE84465), Glioma Longitudinal Analysis Consortium (GLASS), and an immunotherapy trial dataset (GSE121810) were included. RSI-high radioresistant tumors were associated with worse overall survival in TCGA and CGGA than RSI-low tumors. M1/M2 macrophage ratios and RSI scores were inversely associated, indicating that radioresistant glioblastoma tumor microenvironments contain more M2 than M1 macrophages. In the single-cell RNA sequencing dataset, the mean RSI of neoplastic cells was positively correlated with high M2 macrophages proportions. A favorable response to programmed cell death protein 1 (PD-1) therapy was observed in recurrent glioblastomas with high M1/M2 macrophage ratios and low RSI scores. In patients with recurrent glioblastoma, fewer M2 macrophages and low RSI scores were associated with improved overall survival. High M2 macrophage proportions may be involved in radioresistant glioblastoma.