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

Research output: Contribution to journalArticlepeer-review

  • External authors:
  • Colin Hutton
  • Felix Heider
  • Adrian Blanco Gomez
  • Antonia Banyard
  • Alexander Kononov
  • Xiaohong Zhang
  • Saadia A. Karim
  • Viola Paulus-Hock
  • Dale Watt
  • Nina Steele
  • Samantha Kemp
  • Elizabeth Hogg
  • Joanna Kelly
  • Rene-Filip Jackstadt
  • Filipa Lopes
  • Matteo Menotti
  • Luke Chisholm
  • Angela Lamarca
  • Owen J. Sansom
  • Caroline Springer
  • Marina Pasca di Magliano
  • Santiago Zelenay
  • Jennifer P. Morton
  • Claus Jorgensen

Abstract

Fibroblasts display extensive transcriptional heterogeneity, yet functional annotation and characterization of their heterocellular relationships remains incomplete. Using mas 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.

Bibliographical metadata

Original languageEnglish
JournalCancer Cell
Publication statusAccepted/In press - 25 Jun 2021