Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity
Hogg, Elizabeth K. J.
Jackstadt, R. F.
Valle, Juan W
Sansom, O. J.
Pasca di Magliano, M.
Morton, J. P
AffiliationSystems Oncology, Cancer Research UK Manchester Institute, Alderley Park, Manchester SK10 4TG,
MetadataShow full item record
AbstractFibroblasts 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.
CitationHutton C, Heider F, Blanco-Gomez A, Banyard A, Kononov A, Zhang X, et al. Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity. Cancer Cell. 2021 Jul.
- Evidence of two distinct functionally specialized fibroblast lineages in breast stroma.
- Authors: Morsing M, Klitgaard MC, Jafari A, Villadsen R, Kassem M, Petersen OW, Rønnov-Jessen L
- Issue date: 2016 Nov 3
- The carcinoma-associated fibroblast expressing fibroblast activation protein and escape from immune surveillance.
- Authors: Fearon DT
- Issue date: 2014 Mar
- Fibroblast Heterogeneity in the Pancreatic Tumor Microenvironment.
- Authors: Helms E, Onate MK, Sherman MH
- Issue date: 2020 May
- Inter- and intra-tumoural heterogeneity in cancer-associated fibroblasts of human pancreatic ductal adenocarcinoma.
- Authors: Neuzillet C, Tijeras-Raballand A, Ragulan C, Cros J, Patil Y, Martinet M, Erkan M, Kleeff J, Wilson J, Apte M, Tosolini M, Wilson AS, Delvecchio FR, Bousquet C, Paradis V, Hammel P, Sadanandam A, Kocher HM
- Issue date: 2019 May
- Single-cell transcriptome analysis of tumor and stromal compartments of pancreatic ductal adenocarcinoma primary tumors and metastatic lesions.
- Authors: Lin W, Noel P, Borazanci EH, Lee J, Amini A, Han IW, Heo JS, Jameson GS, Fraser C, Steinbach M, Woo Y, Fong Y, Cridebring D, Von Hoff DD, Park JO, Han H
- Issue date: 2020 Sep 29