1. Spatiotemporal Immune Landscape of Colorectal Cancer Liver Metastasis at Single-Cell Level
- Author
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Xiaoying Wang, Jian Zhou, Shuaixi Yang, Shuang-Jian Qiu, Xiaoming Zhang, Fan Bai, Xiao-wu Huang, Qiang Gao, Siyuan Huang, Yifei Liu, Guohe Song, Jiaqiang Ma, Shan Jiang, Yingcheng Wu, Jinxia Liu, Yifei Cheng, Ruibin Xi, Zechuan Chen, Dongning Rao, Jia Fan, and Jianmin Xu
- Subjects
Colorectal cancer ,medicine.medical_treatment ,Cellular level ,Metastasis ,Transcriptome ,Mice ,Spatio-Temporal Analysis ,Immune system ,Tumor Microenvironment ,Animals ,Medicine ,Neoplasm Metastasis ,Mice, Inbred BALB C ,Chemotherapy ,business.industry ,Macrophages ,Liver Neoplasms ,CCL18 ,medicine.disease ,Neoadjuvant Therapy ,Disease Models, Animal ,Oncology ,Cancer research ,Colorectal Neoplasms ,business ,Reprogramming - 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 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, 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 MRC1+ 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. This article is highlighted in the In This Issue feature, p. 1
- Published
- 2022