| Title | Spatiotemporal Immune Landscape of Colorectal Cancer Liver Metastasis at Single-Cell Level |
| Authors | Wu, Yingcheng Yang, Shuaixi Ma, Jiaqiang Chen, Zechuan Song, Guohe Rao, Dongning Cheng, Yifei Huang, Siyuan Liu, Yifei Jiang, Shan Liu, Jinxia Huang, Xiaowu Wang, Xiaoying Qiu, Shuangjian Xu, Jianmin Xi, Ruibin Bai, Fan Zhou, Jian Fan, Jia Zhang, Xiaoming Gao, Qiang |
| Affiliation | Fudan Univ, Zhongshan Hosp, Liver Canc Inst, Dept Liver Surg & Transplantat, 180 Fenglin Rd, Shanghai 200032, Peoples R China Fudan Univ, Liver Canc Inst, Key Lab Carcinogenesis & Canc Invas, Zhongshan Hosp,Minist Educ, Shanghai, Peoples R China Chinese Acad Sci, Ctr Microbes Dev & Hlth, Key Lab Mol Virol & Immunol, Inst Pasteur Shanghai, Shanghai, Peoples R China Peking Univ, Sch Math Sci, Beijing, Peoples R China Peking Univ, Ctr Stat Sci, Beijing, Peoples R China Nantong Univ, Affiliated Hosp, Sch Med, Nantong, Jiangsu, Peoples R China Fudan Univ, Dept Colorectal Surg, Zhongshan Hosp, Shanghai, Peoples R China Fudan Univ, Colorectal Canc Ctr, Zhongshan Hosp, Shanghai, Peoples R China Fudan Univ, Shanghai Engn Res Ctr Colorectal Canc Minimally I, Shanghai, Peoples R China Peking Univ, Sch Life Sci, Biomed Pioneering Innovat Ctr BIOPIC, Beijing, Peoples R China Fudan Univ, Inst Biomed Sci, Key Lab Med Epigenet & Metab, Shanghai, Peoples R China Fudan Univ, State Key Lab Genet Engn, Shanghai, Peoples R China |
| Keywords | MIGRATION INHIBITORY FACTOR T-CELLS GENE HETEROGENEITY COLON CHEMOTHERAPY ACTIVATION SURGERY IMPACT |
| Issue Date | Jan-2022 |
| Publisher | CANCER DISCOVERY |
| Abstract | 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 sequencing and spatial transcriptomics. Strikingly, the metastatic microenvironment underwent remarkable spatial reprogramming of immunosuppressive cells such as MRCP+ 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, whereas the nonresponsive 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. SIGNIFICANCE: We present a single-cell and spatial atlas of colorectal liver metastasis and found the highly metabolically activated MRCP+ CCL18(+) M2-like macrophages in metastatic sites. Efficient neoadjuvant chemotherapy can slow down such metabolic activation, raising the possibility to target metabolism pathways in metastasis. |
| URI | http://hdl.handle.net/20.500.11897/637304 |
| ISSN | 2159-8274 |
| DOI | 10.1158/2159-8290.CD-21-0316 |
| Indexed | SCI(E) |
| Appears in Collections: | 数学科学学院 生命科学学院 |
