IL17A critically shapes the transcriptional program of fibroblasts in pancreatic cancer and switches on their protumorigenic functions.
Adenocarcinoma
/ genetics
Animals
CD8-Positive T-Lymphocytes
/ metabolism
Cancer-Associated Fibroblasts
/ metabolism
Carcinogenesis
/ genetics
Carcinoma, Pancreatic Ductal
/ genetics
Disease Models, Animal
Forkhead Transcription Factors
/ genetics
Humans
Interleukin-17
/ genetics
Mice
Mice, Knockout
Receptors, Interleukin
/ genetics
Tumor Microenvironment
/ genetics
IL17A
cancer-associated fibroblast
extracellular matrix
fibrosis
pancreatic cancer
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
09 02 2021
09 02 2021
Historique:
entrez:
2
2
2021
pubmed:
3
2
2021
medline:
25
6
2021
Statut:
ppublish
Résumé
A hallmark of cancer, including pancreatic ductal adenocarcinoma (PDA), is a massive stromal and inflammatory reaction. Many efforts have been made to identify the anti- or protumoral role of cytokines and immune subpopulations within the stroma. Here, we investigated the role of interleukin-17A (IL17A) and its effect on tumor fibroblasts and the tumor microenvironment. We used a spontaneous PDA mouse model (KPC) crossed to IL17A knockout mice to show an extensive desmoplastic reaction, without impaired immune infiltration. Macrophages, especially CD80
Identifiants
pubmed: 33526692
pii: 2020395118
doi: 10.1073/pnas.2020395118
pmc: PMC8017922
pii:
doi:
Substances chimiques
Forkhead Transcription Factors
0
Foxp3 protein, mouse
0
Il17a protein, mouse
0
Il17rc protein, mouse
0
Interleukin-17
0
Receptors, Interleukin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare no competing interest.
Références
J Clin Invest. 2020 Sep 1;130(9):4704-4709
pubmed: 32749238
Proc Natl Acad Sci U S A. 2019 Feb 26;116(9):3604-3613
pubmed: 30733286
Microsc Res Tech. 2009 Jun;72(6):411-23
pubmed: 19208388
Pancreas. 2004 Jan;28(1):e26-31
pubmed: 14707745
Gastroenterology. 2018 Jul;155(1):210-223.e3
pubmed: 29604293
Thorac Cancer. 2020 Jan;11(1):120-129
pubmed: 31760702
PLoS One. 2017 Nov 30;12(11):e0188870
pubmed: 29190794
J Exp Med. 2020 Dec 7;217(12):
pubmed: 32860704
Oncotarget. 2016 Nov 15;7(46):76197-76213
pubmed: 27776346
Nat Immunol. 2013 Oct;14(10):1014-22
pubmed: 24048123
Cancer Lett. 2009 Jun 28;279(1):1-7
pubmed: 19013709
Gastroenterology. 2013 May;144(5):1098-106
pubmed: 23333712
Mech Ageing Dev. 2011 Oct;132(10):468-79
pubmed: 21820463
Cancer Cell. 2014 Jun 16;25(6):719-34
pubmed: 24856586
Clin Cancer Res. 2007 Sep 15;13(18 Pt 2):5549s-5555s
pubmed: 17875788
Cancer Cell. 2014 Jun 16;25(6):735-47
pubmed: 24856585
Cancer Cell. 2014 May 12;25(5):621-37
pubmed: 24823639
J Exp Med. 2015 Mar 9;212(3):333-49
pubmed: 25732306
Gut. 2017 Nov;66(11):1995-2007
pubmed: 27464707
Proc Natl Acad Sci U S A. 2019 Mar 5;116(10):4326-4335
pubmed: 30770442
J Exp Med. 2017 Mar 6;214(3):579-596
pubmed: 28232471
Cancer Cell. 2020 Mar 16;37(3):289-307.e9
pubmed: 32183949
Immunity. 2002 Sep;17(3):375-87
pubmed: 12354389
Gastroenterology. 2018 Mar;154(4):820-838
pubmed: 29287624
Cancer Discov. 2019 Aug;9(8):1102-1123
pubmed: 31197017
Oncoimmunology. 2017 Nov 13;7(2):e1393596
pubmed: 29308326
BMC Cancer. 2014 Jul 09;14:499
pubmed: 25011545
Growth Horm IGF Res. 2005 Jun;15(3):185-92
pubmed: 15914054
Cancer Immunol Immunother. 2013 Jul;62(7):1249-60
pubmed: 23640603
Cancer Microenviron. 2015 Dec;8(3):159-66
pubmed: 25106539
Clin Gastroenterol Hepatol. 2008 Oct;6(10):1155-61
pubmed: 18639493
Nat Rev Cancer. 2016 Aug 23;16(9):582-98
pubmed: 27550820
HPB (Oxford). 2015 Apr;17(4):292-8
pubmed: 25250696
J Clin Invest. 2016 Nov 1;126(11):4140-4156
pubmed: 27701147
Cell. 2019 Jun 13;177(7):1888-1902.e21
pubmed: 31178118
Gastroenterology. 2015 Jul;149(1):201-10
pubmed: 25888329
Cancer Immunol Immunother. 2018 Jun;67(6):981-988
pubmed: 28884365
Gastroenterology. 2013 Jun;144(6):1210-9
pubmed: 23622130
Br J Cancer. 2014 Nov 11;111(10):1917-23
pubmed: 25314063
Cancer Res. 2003 Dec 15;63(24):8912-21
pubmed: 14695208
Gut. 2015 Sep;64(9):1476-84
pubmed: 25994217