肿瘤微环境
免疫系统
脑转移
转录组
转移
肺癌
癌症研究
脑瘤
小胶质细胞
原发性肿瘤
肺
癌症
医学
生物
病理
炎症
免疫学
基因表达
基因
内科学
生物化学
作者
Qi Zhang,Rober Abdo,Cristiana Iosef,Tomonori Kaneko,Matthew J. Cecchini,Victor Han,Shawn Shun‐Cheng Li
标识
DOI:10.1038/s41467-022-33365-y
摘要
Brain metastases (BrMs) are a common occurrence in lung cancer with a dismal outcome. To understand the mechanism of metastasis to inform prognosis and treatment, here we analyze primary and metastasized tumor specimens from 44 non-small cell lung cancer patients by spatial RNA sequencing, affording a whole transcriptome map of metastasis resolved with morphological markers for the tumor core, tumor immune microenvironment (TIME), and tumor brain microenvironment (TBME). Our data indicate that the tumor microenvironment (TME) in the brain, including the TIME and TBME, undergoes extensive remodeling to create an immunosuppressive and fibrogenic niche for the BrMs. Specifically, the brain TME is characterized with reduced antigen presentation and B/T cell function, increased neutrophils and M2-type macrophages, immature microglia, and reactive astrocytes. Differential gene expression and network analysis identify fibrosis and immune regulation as the major functional modules disrupted in both the lung and brain TME. Besides providing systems-level insights into the mechanism of lung cancer brain metastasis, our study uncovers potential prognostic biomarkers and suggests that therapeutic strategies should be tailored to the immune and fibrosis status of the BrMs.
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