Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity

Cancer Cell. 2021 Sep 13;39(9):1227-1244.e20. doi: 10.1016/j.ccell.2021.06.017. Epub 2021 Jul 22.


Fibroblasts display extensive transcriptional heterogeneity, yet functional annotation and characterization of their heterocellular relationships remains incomplete. Using mass cytometry, we chart the stromal composition of 18 murine tissues and 5 spontaneous tumor models, with an emphasis on mesenchymal phenotypes. This analysis reveals extensive stromal heterogeneity across tissues and tumors, and identifies coordinated relationships between mesenchymal and immune cell subsets in pancreatic ductal adenocarcinoma. Expression of CD105 demarks two stable and functionally distinct pancreatic fibroblast lineages, which are also identified in murine and human healthy tissues and tumors. Whereas CD105-positive pancreatic fibroblasts are permissive for tumor growth in vivo, CD105-negative fibroblasts are highly tumor suppressive. This restrictive effect is entirely dependent on functional adaptive immunity. Collectively, these results reveal two functionally distinct pancreatic fibroblast lineages and highlight the importance of mesenchymal and immune cell interactions in restricting tumor growth.

Keywords: CAF; CD105; CyTOF; Eng; cancer-associated fibroblast lineages; mass cytometry; pancreatic cancer; tumor microenvironment; tumor-restrictive fibroblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Cancer-Associated Fibroblasts / immunology*
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / immunology*
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Plasticity
  • Endoglin / genetics*
  • Endoglin / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / immunology*
  • Single-Cell Analysis / methods*
  • Tumor Microenvironment


  • ENG protein, human
  • Endoglin