Spatiotemporal Immune Landscape of Colorectal Cancer Liver Metastasis at Single-Cell Level.

By Yingcheng Wu, Shuaixi Yang, Jiaqiang Ma, Zechuan Chen, Guohe Song, D. Rao, Yifei Cheng, Siyuan Huang, Yifei Liu, Shan Jiang and 11 more. Cancer Discovery, 2021

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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.

Subfields: Immunology, Molecular Biology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/274a30c94118e5d3f0e661c1ff01a4e865bca3f5