2021/08/20 by Yingcheng Wu, Shuaixi Yang, Jiaqiang Ma +18 · 7 citations
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · Medicine · #Ferroptosis and cancer prognosis #Immune cells in cancer #Single-cell and spatial transcriptomics
paper · pdf · doi:10.1158/2159-8290.cd-21-0316
openalex publication_date 2021/08/20 · openalex created_date 2021/08/30 · openalex updated_date 2026/07/30
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