Single-cell RNA sequencing reveals cellular and molecular reprograming landscape of gliomas and lung cancer brain metastases.

in Clinical and translational medicine by He-Fen Sun, Liang-Dong Li, I-Weng Lao, Xuan Li, Bao-Jin Xu, Yi-Qun Cao, Wei Jin

TLDR

  • The study looked at the cells in the brain that came from a type of lung cancer called LUAD. They used a special tool called single-cell RNA sequencing to see how these cells were different from each other. They found that the cells in LC were different from the cells in gliomas in many ways. They also found that some cells in LC were making a substance that helped the cancer grow. They also found that some cells in LC were communicating with other cells to help the cancer grow. The study provides important information that could help doctors develop new treatments for brain metastasis of lung cancer.

Abstract

Brain malignancies encompass gliomas and brain metastases originating from extracranial tumours including lung cancer. Approximately 50% of patients with lung adenocarcinoma (LUAD) will eventually develop brain metastases. However, the specific characteristics of gliomas and lung-to-brain metastases (LC) are largely unknown. We applied single-cell RNA sequencing to profile immune and nonimmune cells in 4 glioma and 10 LC samples. Our analysis revealed that tumour microenvironment (TME) cells are present in heterogeneous subpopulations. LC reprogramed cells into immune suppressed state, including microglia, macrophages, endothelial cells, and CD8T cells, with unique cell proportions and gene signatures. Particularly, we identified that a subset of macrophages was associated with poor prognosis. ROS (reactive oxygen species)-producing neutrophils was found to participant in angiogenesis. Furthermore, endothelial cells participated in active communication with fibroblasts. Metastatic epithelial cells exhibited high heterogeneity in chromosomal instability (CIN) and cell population. Our findings provide a comprehensive understanding of the heterogenicity of the tumor microenvironment and tumour cells and it will be crucial for successful immunotherapy development for brain metastasis of lung cancer.

Overview

  • The study aims to understand the characteristics of gliomas and lung-to-brain metastases (LC) using single-cell RNA sequencing. The study profiles immune and nonimmune cells in 4 glioma and 10 LC samples. The primary objective is to identify the heterogeneity of the tumor microenvironment and tumor cells in LC and its impact on immunotherapy development for brain metastasis of lung cancer.

Comparative Analysis & Findings

  • The study reveals that LC reprograms cells into an immune suppressed state, including microglia, macrophages, endothelial cells, and CD8T cells, with unique cell proportions and gene signatures. A subset of macrophages was associated with poor prognosis. ROS-producing neutrophils participated in angiogenesis. Endothelial cells participated in active communication with fibroblasts. Metastatic epithelial cells exhibited high heterogeneity in chromosomal instability (CIN) and cell population.

Implications and Future Directions

  • The study's findings provide a comprehensive understanding of the heterogenicity of the tumor microenvironment and tumor cells in LC, which is crucial for successful immunotherapy development for brain metastasis of lung cancer. Future research should focus on identifying specific immune cells and their roles in LC and developing targeted immunotherapies to modulate these cells.
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