Single-cell analysis uncovers liver susceptibility to pancreatic cancer metastasis via myeloid cell characterization

作者：Aizier Ainiwaer, Zhenwei Qian, Jianxun Wang, Qi Zhao, Yinying Lu · 发表于：Discover Oncology · 年份：2024 · DOI：10.1007/s12672-024-01566-0 · 被引用次数：5 · 研究领域：Pancreatic and Hepatic Oncology Research、Immune cells in cancer、Single-cell and spatial transcriptomics

The liver is the predominant metastatic site for diverse cancers, including pancreatic and colorectal cancers (CRC), etc. The high incidence of hepatic metastasis of pancreatic cancer is an important reason for its refractory and high mortality. Therefore, it is important to understand how metastatic pancreatic cancer affects the hepatic tumor immune microenvironment (TME) in patients. Here, we characterized the TME of liver metastases unique to pancreatic cancer by comparing them with CRC liver metastases. We integrated two single-cell RNA-seq (scRNA-seq) datasets including tumor samples of pancreatic cancer liver metastasis (P-LM), colorectal cancer liver metastasis (C-LM), primary pancreatic cancer (PP), primary colorectal cancer (PC), as well as samples of peripheral blood mono-nuclear cells (PBMC), adjacent normal pancreatic tissues (NPT), to better characterize the heterogeneities of the microenvironment of two kinds of liver metastases. We next performed comparative analysis on cellular compositions between P-LM and C-LM, found that Mph_SPP1, a subset of macrophages associated with angiogenesis and tumor invasion, was more enriched in the P-LM group, indicating this kind of macrophages provide a TME niche more vulnerable for pancreatic cancers. Analysis of the developmental trajectory implied that Mph_SPP1 may progressively be furnished with increased expression of genes regulating endothelium. Cell-cell communications analysis revealed that Mph_SPP1 potentially intera...