Single cell transcriptomic analyses implicate an immunosuppressive tumor microenvironment in pancreatic cancer liver metastasis

Shu Zhang, Wen Fang, Siqi Zhou, Dongming Zhu, Ruidong Chen, Xin Gao, Zhuojin Li, Yao Fu, Yixuan Zhang, Fa Yang, Jing Zhao, Hao Wu, Pin Wang, Yonghua Shen, Shanshan Shen, Guifang Xu, Lei Wang, Chao Yan (), Xiaoping Zou (), Dijun Chen () and Ying Lv ()
Additional contact information
Shu Zhang: The Affiliated Hospital of Nanjing University Medical School
Wen Fang: Nanjing University
Siqi Zhou: Nanjing Drum Tower Hospital Clinical College of Jiangsu University
Dongming Zhu: The First Affiliated Hospital of Soochow University
Ruidong Chen: Nanjing University
Xin Gao: The First Affiliated Hospital of Soochow University
Zhuojin Li: Nanjing University
Yao Fu: The Affiliated Hospital of Nanjing University Medical School
Yixuan Zhang: The Affiliated Hospital of Nanjing University Medical School
Fa Yang: Nanjing University
Jing Zhao: The Affiliated Hospital of Nanjing University Medical School
Hao Wu: The Affiliated Hospital of Nanjing University Medical School
Pin Wang: The Affiliated Hospital of Nanjing University Medical School
Yonghua Shen: The Affiliated Hospital of Nanjing University Medical School
Shanshan Shen: The Affiliated Hospital of Nanjing University Medical School
Guifang Xu: The Affiliated Hospital of Nanjing University Medical School
Lei Wang: The Affiliated Hospital of Nanjing University Medical School
Chao Yan: Nanjing University Institute of Pancreatology
Xiaoping Zou: The Affiliated Hospital of Nanjing University Medical School
Dijun Chen: Nanjing University Institute of Pancreatology
Ying Lv: The Affiliated Hospital of Nanjing University Medical School

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease refractory to all targeted and immune therapies. However, our understanding of PDAC microenvironment especially the metastatic microenvironment is very limited partly due to the inaccessibility to metastatic tumor tissues. Here, we present the single-cell transcriptomic landscape of synchronously resected PDAC primary tumors and matched liver metastases. We perform comparative analysis on both cellular composition and functional phenotype between primary and metastatic tumors. Tumor cells exhibit distinct transcriptomic profile in liver metastasis with clearly defined evolutionary routes from cancer cells in primary tumor. We also identify specific subtypes of stromal and immune cells critical to the formation of the pro-tumor microenvironment in metastatic lesions, including RGS5+ cancer-associated fibroblasts, CCL18+ lipid-associated macrophages, S100A8+ neutrophils and FOXP3+ regulatory T cells. Cellular interactome analysis further reveals that the lack of tumor-immune cell interaction in metastatic tissues contributes to the formation of the immunosuppressive microenvironment. Our study provides a comprehensive characterization of the transcriptional landscape of PDAC liver metastasis.

Date: 2023
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DOI: 10.1038/s41467-023-40727-7

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