Single-Cell RNA-Sequencing Shift in the Interaction Pattern Between Glioma Stem Cells and Immune Cells During Tumorigenesis

Abstract

Glioblastoma is one of the most common neoplasms in the central nervous system characterized by limited immune response and unlimited expansion capability. Cancer stem cells (GSCs), a small fraction of the tumor cells, possess a pivotal regulation capability in the tumor microenvironment with a superior proliferation ability. We aimed to reveal the interaction between glioma stem cells (GSCs) and immune cells during tumorigenesis. Single-cell sequencing data from seven surgical specimens of glioblastoma patients and patient-derived GSCs cocultured with peripheral leukocytes were used for the analysis. Cell grouping and trajectory analysis were performed using Seurat and Monocle 3 packages in R software. The gene set of Cancer Genome Anatomy Project was used to define different cell types. Cells with the ability of proliferation and differentiation in glioblastoma tissue were defined as GSCs, which had a similar expression pattern to that in the GSCs in vitro. Astrocytes in glioblastoma were mainly derived from differentiated GSCs, while oligodendrocytes were most likely to be derived from different precursor cells. No remarkable evolutionary trajectory was observed among the subgroups of T cells in glioblastoma. The immune checkpoint interaction between GSCs and immune cells was changed from stimulatory to inhibitory during tumorigenesis. The patient-derived GSCs system is an ideal model for GSC research. The above research revealed that the interaction pattern between GSC glioma stem cells and immune cells during tumorigenesis provides a theoretical basis for GSC glioma stem cell-targeted immunotherapy.