دورية أكاديمية
Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity.
| العنوان: | Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity. |
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| المؤلفون: | Hutton C; Systems Oncology, Cancer Research UK Manchester Institute, Alderley Park, Manchester SK10 4TG, UK., Heider F; Systems Oncology, Cancer Research UK Manchester Institute, Alderley Park, Manchester SK10 4TG, UK., Blanco-Gomez A; Systems Oncology, Cancer Research UK Manchester Institute, Alderley Park, Manchester SK10 4TG, UK., Banyard A; Flow Cytometry Core, Cancer Research UK Manchester Institute, Alderley Park, Manchester SK10 4TG, UK., Kononov A; Systems Oncology, Cancer Research UK Manchester Institute, Alderley Park, Manchester SK10 4TG, UK., Zhang X; Systems Oncology, Cancer Research UK Manchester Institute, Alderley Park, Manchester SK10 4TG, UK., Karim S; Cancer Research UK Beatson Institute, Garscube Estate, Bearsden, Glasgow G61 1BD, UK., Paulus-Hock V; Cancer Research UK Beatson Institute, Garscube Estate, Bearsden, Glasgow G61 1BD, UK., Watt D; Cancer Research UK Beatson Institute, Garscube Estate, Bearsden, Glasgow G61 1BD, UK., Steele N; University of Michigan, Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA; Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA; Department of Cell and Developmental Biology, Ann Arbor, MI 48109, USA., Kemp S; Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA; Molecular and Cellular Pathology Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA., Hogg EKJ; Systems Oncology, Cancer Research UK Manchester Institute, Alderley Park, Manchester SK10 4TG, UK., Kelly J; Systems Oncology, Cancer Research UK Manchester Institute, Alderley Park, Manchester SK10 4TG, UK., Jackstadt RF; Cancer Research UK Beatson Institute, Garscube Estate, Bearsden, Glasgow G61 1BD, UK., Lopes F; Drug Discovery Unit, Cancer Research UK Manchester Institute, Alderley Park, Manchester SK10 4TG, UK., Menotti M; Cell Signalling, Cancer Research UK Manchester Institute, Alderley Park, Manchester SK10 4TG, UK., Chisholm L; Molecular Oncology, Cancer Research UK Manchester Institute, Alderley Park, Manchester SK10 4TG, UK., Lamarca A; Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK., Valle J; Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK; Institute of Cancer Sciences, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK., Sansom OJ; Cancer Research UK Beatson Institute, Garscube Estate, Bearsden, Glasgow G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, Switchback Road, Garscube Estate, Glasgow G61 1QH, UK., Springer C; Drug Discovery Unit, Cancer Research UK Manchester Institute, Alderley Park, Manchester SK10 4TG, UK., Malliri A; Cell Signalling, Cancer Research UK Manchester Institute, Alderley Park, Manchester SK10 4TG, UK., Marais R; Molecular Oncology, Cancer Research UK Manchester Institute, Alderley Park, Manchester SK10 4TG, UK., Pasca di Magliano M; University of Michigan, Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA; Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA., Zelenay S; Cancer Immunity and Inflammation, Cancer Research UK Manchester Institute, Alderley Park, Manchester SK10 4TG, UK., Morton JP; Cancer Research UK Beatson Institute, Garscube Estate, Bearsden, Glasgow G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, Switchback Road, Garscube Estate, Glasgow G61 1QH, UK., Jørgensen C; Systems Oncology, Cancer Research UK Manchester Institute, Alderley Park, Manchester SK10 4TG, UK. Electronic address: claus.jorgensen@cruk.manchester.ac.uk. |
| المصدر: | Cancer cell [Cancer Cell] 2021 Sep 13; Vol. 39 (9), pp. 1227-1244.e20. Date of Electronic Publication: 2021 Jul 22. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101130617 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-3686 (Electronic) Linking ISSN: 15356108 NLM ISO Abbreviation: Cancer Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, Mass. : Cell Press, c2002- |
| مواضيع طبية MeSH: | Cancer-Associated Fibroblasts/*immunology , Carcinoma, Pancreatic Ductal/*immunology , Endoglin/*genetics , Pancreatic Neoplasms/*immunology , Single-Cell Analysis/*methods, Adaptive Immunity ; Animals ; Carcinoma, Pancreatic Ductal/genetics ; Case-Control Studies ; Cell Line, Tumor ; Cell Plasticity ; Endoglin/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Mice ; Neoplasm Transplantation ; Pancreatic Neoplasms/genetics ; Tumor Microenvironment |
| مستخلص: | 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. Competing Interests: Declaration of interests O.S. receives funding from Novartis, AstraZeneca, RedEx and Cancer Research Technology. C.J. receives funding from AstraZeneca. R.M. is an expert witness for Pfizer and, as a former employee of the Institute of Cancer Research (ICR) in London, may benefit financially from commercialized programs. C.S. and F.L. are former employees of the ICR in London and may benefit financially from commercialized programs. The other authors declare no competing interests. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.) |
| التعليقات: | Comment in: Cancer Cell. 2021 Sep 13;39(9):1175-1177. (PMID: 34520729) |
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| معلومات مُعتمدة: | A25236 United Kingdom CRUK_ Cancer Research UK; C5759/A27412 United Kingdom CRUK_ Cancer Research UK; 21139 United Kingdom CRUK_ Cancer Research UK; 20410 United Kingdom CRUK_ Cancer Research UK; A17196 United Kingdom CRUK_ Cancer Research UK; 19258 United Kingdom CRUK_ Cancer Research UK; 22255 United Kingdom CRUK_ Cancer Research UK; A21139 United Kingdom CRUK_ Cancer Research UK; 22902 United Kingdom CRUK_ Cancer Research UK; 17098 United Kingdom CRUK_ Cancer Research UK; 29996 United Kingdom CRUK_ Cancer Research UK; A29996 United Kingdom CRUK_ Cancer Research UK |
| فهرسة مساهمة: | Keywords: CAF; CD105; CyTOF; Eng; cancer-associated fibroblast lineages; mass cytometry; pancreatic cancer; tumor microenvironment; tumor-restrictive fibroblasts |
| المشرفين على المادة: | 0 (ENG protein, human) 0 (Endoglin) |
| تواريخ الأحداث: | Date Created: 20210723 Date Completed: 20220105 Latest Revision: 20240210 |
| رمز التحديث: | 20240210 |
| مُعرف محوري في PubMed: | PMC8443274 |
| DOI: | 10.1016/j.ccell.2021.06.017 |
| PMID: | 34297917 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1878-3686 |
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| DOI: | 10.1016/j.ccell.2021.06.017 |