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Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity
Hutton, Colin Heider, Felix Blanco-Gomez, Adrian Banyard, Antonia Kononov, Alexander Zhang, Xiaohong Karim, S. Paulus-Hock, V. Watt, D. Steele, N.
Hutton, Colin
Heider, Felix
Blanco-Gomez, Adrian
Banyard, Antonia
Kononov, Alexander
Zhang, Xiaohong
Karim, S.
Paulus-Hock, V.
Watt, D.
Steele, N.
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Abstract
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.
Authors
Hutton, Colin
Heider, Felix
Blanco-Gomez, Adrian
Banyard, Antonia
Kononov, Alexander
Zhang, Xiaohong
Karim, S.
Paulus-Hock, V.
Watt, D.
Steele, N.
Kemp, S.
Hogg, Elizabeth K. J.
Kelly, Joanna
Jackstadt, R. F.
Lopes, Filipa
Menotti, Matteo
Chisholm, Luke
Lamarca, Angela
Valle, Juan W
Sansom, O. J.
Springer, Caroline
Malliri, Angeliki
Marais, Richard
Pasca di Magliano, M.
Zelenay, Santiago
Morton, J. P
Jørgensen, Claus
Heider, Felix
Blanco-Gomez, Adrian
Banyard, Antonia
Kononov, Alexander
Zhang, Xiaohong
Karim, S.
Paulus-Hock, V.
Watt, D.
Steele, N.
Kemp, S.
Hogg, Elizabeth K. J.
Kelly, Joanna
Jackstadt, R. F.
Lopes, Filipa
Menotti, Matteo
Chisholm, Luke
Lamarca, Angela
Valle, Juan W
Sansom, O. J.
Springer, Caroline
Malliri, Angeliki
Marais, Richard
Pasca di Magliano, M.
Zelenay, Santiago
Morton, J. P
Jørgensen, Claus
Description
Date
2021
Publisher
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Type
Article
Citation
Hutton 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.