Single-cell RNA sequencing reveals cellular and molecular reprograming landscape of brain tumors

Brain malignancies encompass gliomas and brain metastases originating from extracranial tumors. To reveal the specific characteristics of gliomas and lung-to-brain metastases (LC), we applied single-cell RNA sequencing to profile immune and nonimmune cells in glioma and LC samples. Our analysis revealed that immune cells are present in heterogeneous subpopulations and that LC reprograms cells, including microglia, macrophages, neutrophils, endothelial cells, and T cells, with unique cell proportions and gene signatures. Particularly, we identified that a subset of macrophages was associated with poor prognosis. In addition, ROS-producing neutrophils was found to play an important role in angiogenesis. Furthermore, endothelial cells participated in active communication with fibroblasts. Metastatic epithelial cells exhibited heterogeneity in DNA copy number variation and we identified one subpopulation with stem cell-like phenotype. Further understanding of the heterogenicity of the tumor microenvironment and tumor cells will be crucial for successful immunotherapy development for lung cancer. Single-cell RNA sequencing analysiss of 4 gliomas and 10 lung-to-brain metastases by BD Rhapsody system.