Single cell RNA sequencing reveals heterogenous immune landscape of tumor infiltrated immune cell population against glioblastoma

Glioblastoma (GBM) is the most aggressive glioma. Recently, immunotherapy using immune-checkpoint blockage (ICB) has provided therapeutic efficacy to various tumors. Despite an attractive ICB therapy, there have not been beneficial outcomes about GBM patients due to the characteristic of immunosuppressive environment. Thus, it is essential to understand the features of GBM immune microenvironment. Here, we profile immune cells of GBM microenvironment via single cell RNA sequencing (scRNAseq) according to GBM progression in orthotopic glioma model. We identify that kinetics of immune cell population throughout the GBM: macrophages are recruited first and T cells are recruited later. In addition, we analyze early and late stage of microglia and macrophages. Especially, GBM progression down-regulates pro-inflammatory genes and interferon responsive genes in microglia and induces M2 phenotype of recruited macrophages. We further identify that at later stage, overall T cells are increased, but regulatory T cells (Tregs) are significantly increased. In particular, CD8T cells express Nur77 but they also increase multiple inhibitory molecules and show reduction of effector molecules. These findings reveal overall profiling and features of immune cells in GBM microenvironment and provide comprehensive landscape of immune cells throughout GBM progression.