Single cell transcriptomic analyses implicate an immunosuppressive tumormicroenvironment in pancreatic cancer liver metastasis.

Zhang S, Fang W#, Zhou S, Zhu D, Chen R#,Gao X, Li Z, Fu Y, Zhang Y, Yang F, Zhao J, Wu H, WangP, Shen Y, Shen S, Xu G, Wang L, Yan C, Zou X, Chen D*, Lv Y
Nat Commun. 2023 Aug 23;14(1):5123. doi: 10.1038/s41467-023-40727-7.

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic diseaserefractory to all targeted and immune therapies. However, our understanding ofPDAC microenvironment especially the metastatic microenvironment is very limitedpartly due to the inaccessibility to metastatic tumor tissues. Here, we presentthe single-cell transcriptomic landscape of synchronously resected PDAC primarytumors and matched liver metastases. We perform comparative analysis on bothcellular composition and functional phenotype between primary and metastatictumors. Tumor cells exhibit distinct transcriptomic profile in liver metastasiswith clearly defined evolutionary routes from cancer cells in primary tumor. Wealso identify specific subtypes of stromal and immune cells critical to theformation of the pro-tumor microenvironment in metastatic lesions, includingRGS5+ cancer-associated fibroblasts, CCL18+ lipid-associated macrophages,S100A8+ neutrophils and FOXP3+ regulatory T cells. Cellular interactome analysisfurther reveals that the lack of tumor-immune cell interaction in metastatictissues contributes to the formation of the immunosuppressive microenvironment.Our study provides a comprehensive characterization of the transcriptionallandscape of PDAC liver metastasis.

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School of Life Sciences, Nanjing University
Nanjing 210023, China

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