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

• DOI: 10.1016/j.ccell.2021.06.017
• Publication Date: 2021-07-22T14:40:18Z
• Authors: Colin Hutton; Felix Heider; Adrian Blanco-Gomez; Antonia Banyard; Alexander Kononov; Xiaohong Zhang; Saadia Karim; Viola Paulus-Hock; Dale Watt; Nina Steele; Samantha Kemp; Elizabeth K.J. Hogg; Joanna Kelly; Rene-Filip Jackstadt; Filipa Lopes; Matteo Menotti; Luke Chisholm; Angela Lamarca; Juan Valle; Owen J. Sansom; Caroline Springer; Angeliki Malliri; Richard Marais; Marina Pasca di M...; Santiago Zelenay; Jennifer P. Morton; Claus Jørgensen
• Keywords: Pancreatic tumor

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