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

Abstract

Background 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. Methods We applied single‐cell RNA sequencing to profile immune and nonimmune cells in 4 glioma and 10 LC samples. Results 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 CD8+ T 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. Conclusions 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.

Identification of distinct tumor cell patterns with single-cell RNA sequencing integrating primary lung adenocarcinoma and brain metastasis tumor

“…Cancer cells and cells in the tumor microenvironment collectively determine disease progression and response or avoidance to treatment ( 10 ). scRNA-seq including glioma and LUAD brain metastasis mainly focus on the non-tumor cells reported LUAD BM reprogramed cells into immune suppressed state, and immunotherapy could potentially an effective treatment ( 48 ). Study on tumor cell at cell level may provide target of tumor cells, combined with immunotherapy which may improve treatment efficacy.…”

scRNA‐seq and proteomics reveal the distinction of M2‐like macrophages between primary and recurrent malignant glioma and its critical role in the recurrence

“…BD Rhapsody system (BD Biosciences) was used to obtain the single‐cell transcriptomic expression profile from glioma tissues in accordance with the protocol provided by the manufacturer, and the details were described in the previous study 14 . In short, immediately after the resection by professional neurosurgeons, fresh tumor tissue specimens were rapidly transported to the lab on ice, followed by mincing, digesting, and suspending.…”

Targeting of endothelial cells in brain tumours

“…These neutrophils exhibit activated HIF-1 signalling pathways by expressing HIF1A, lactate dehydrogenase A, VEGF-A, which are significant pro-angiogenic factors. 61 Taken together, angio-genesis is the result of the interaction of multiple TME components. Thus, targeting the TME may provide new ideas for the anti-angiogenic approaches.…”

“…A recent single‐cell sequencing‐based study showed a neutrophil cluster characterised by reactive oxygen species‐production in the lung cancer brain metastasis microenvironment. These neutrophils exhibit activated HIF‐1 signalling pathways by expressing HIF1A, lactate dehydrogenase A, VEGF‐A, which are significant pro‐angiogenic factors 61 . Taken together, angiogenesis is the result of the interaction of multiple TME components.…”