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][1] [1]: /lookup/volpage/12/1?iss=1

中文翻译：

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单细胞水平结直肠癌肝转移的时空免疫景观

肝转移是结直肠癌死亡的主要原因，表现出高度异质性和抑制性免疫微环境。在这里，我们使用单细胞 RNA 测序和空间转录组学对 97 个匹配的样本进行了测序。引人注目的是，转移性微环境经历了免疫抑制细胞（如 MRC1 + CCL18 + M2 样巨噬细胞）的显着空间重编程。我们进一步开发了 scMetabolism，一种用于量化单细胞代谢的计算管道，并观察到这些巨噬细胞具有增强的代谢活性。有趣的是，新辅助化疗可以阻断这种状态并恢复有反应患者的抗肿瘤免疫平衡，而无反应患者则恶化为更具抑制性的患者。我们的工作描述了转移的免疫进化，并揭示了肿瘤如何对新辅助化疗作出反应的黑匣子。意义：我们提出了结直肠肝转移的单细胞和空间图谱，并在转移部位发现了高度代谢激活的 MRC1 + CCL18 + M2 样巨噬细胞。有效的新辅助化疗可以减缓这种代谢激活，提高靶向转移代谢途径的可能性。本文在 In This Issue 功能中突出显示，[p. 1][1][1]：/lookup/volpage/12/1?iss=1 有效的新辅助化疗可以减缓这种代谢激活，提高靶向转移代谢途径的可能性。本文在 In This Issue 功能中突出显示，[p. 1][1][1]：/lookup/volpage/12/1?iss=1 有效的新辅助化疗可以减缓这种代谢激活，提高靶向转移代谢途径的可能性。本文在 In This Issue 功能中突出显示，[p. 1][1][1]：/lookup/volpage/12/1?iss=1