Spatiotemporal Immune Landscape of Colorectal Cancer Liver Metastasis at Single-Cell Level.
Yingcheng WuShuaixi YangJiaqiang MaZechuan ChenGuohe SongDongning RaoYifei ChengSiyuan HuangYifei LiuShan JiangJinxia LiuXiaowu HuangXiaoying WangShuangjian QiuJian-Ming XuRuibin XiFan BaiJian ZhouJia FanXiaoming ZhangQiang GaoPublished in: Cancer discovery (2021)
Liver metastasis, the leading cause of colorectal cancer mortality, exhibits a highly heterogeneous and suppressive immune microenvironment. Here, we sequenced 97 matched samples by using single-cell RNA-seq and Spatial Transcriptomics. Strikingly, metastatic microenvironment underwent remarkable spatial reprogramming of immunosuppressive cells such as MRC1+ CCL18+ M2-like macrophages. We further developed scMetabolism, a computational pipeline for quantifying single-cell metabolism, and observed that those macrophages harbored enhanced metabolic activity. Interestingly, neoadjuvant chemotherapy could block this status and restore the antitumor immune balance in responsive patients, while the non-responsive patients deteriorated into a more suppressive one. Our work described the immune evolution of metastasis and uncovered the black box of how tumors respond to neoadjuvant chemotherapy.
Keyphrases
- single cell
- rna seq
- neoadjuvant chemotherapy
- end stage renal disease
- ejection fraction
- locally advanced
- newly diagnosed
- high throughput
- chronic kidney disease
- lymph node
- stem cells
- prognostic factors
- small cell lung cancer
- sentinel lymph node
- induced apoptosis
- radiation therapy
- early stage
- cancer therapy
- patient reported outcomes
- oxidative stress
- risk factors
- rectal cancer
- liver injury
- cell cycle arrest