Chemokine Receptor Expression on T Cells Is Modulated by CAFs and Chemokines Affect the Spatial Distribution of T Cells in Pancreatic Tumors.

CCR5 CD4 T cells CD8 T cells CXCR3 CXCR4 carcinoma-associated fibroblasts chemokines pancreatic cancer

Journal

Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829

Informations de publication

Date de publication:
06 Aug 2022
Historique:
received: 20 04 2022
revised: 21 07 2022
accepted: 03 08 2022
entrez: 12 8 2022
pubmed: 13 8 2022
medline: 13 8 2022
Statut: epublish

Résumé

The accumulation of T cells is associated with a better prognosis in pancreatic cancer. However, the immunosuppressive tumor microenvironment, largely composed by cancer-associated fibroblasts (CAFs), can prevent T cells from reaching the tumor nests. We examined how human CAFs modulated chemokine receptors known to be associated with T cell trafficking, CXCR3 and CCR5, and T cell exclusion, CXCR4. CAFs decreased the expression of CXCR3 and CCR5 but increased CXCR4 expression in both 2D and 3D cultures, affecting the migratory capacity of T cells towards CXCL10. An immunohistochemistry analysis showed that very few T cells were found in the tumor nests. Within the stroma, CD8

Identifiants

pubmed: 35954489
pii: cancers14153826
doi: 10.3390/cancers14153826
pmc: PMC9367555
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Swedish Cancer Foundation
ID : 20 1162 PjF
Organisme : Cancer Society in Stockholm
ID : 201152
Organisme : Cancer and Allergy Foundation
ID : 10388

Références

Cancer Immunol Immunother. 2015 Dec;64(12):1553-63
pubmed: 26423423
Pharmacol Ther. 2017 Nov;179:158-170
pubmed: 28549596
Sci Rep. 2017 Dec 4;7(1):16878
pubmed: 29203879
Sci Rep. 2020 Oct 15;10(1):17444
pubmed: 33060625
Front Pharmacol. 2020 Dec 08;11:574667
pubmed: 33363463
Nat Commun. 2015 Jun 25;6:7458
pubmed: 26109379
Cancer Med. 2017 Feb;6(2):463-470
pubmed: 28097809
Cancer Res. 2007 Oct 1;67(19):9518-27
pubmed: 17909062
Clin Cancer Res. 2019 Jul 1;25(13):3934-3945
pubmed: 30940657
J Leukoc Biol. 2003 Nov;74(5):791-9
pubmed: 12960247
Am J Pathol. 2010 Mar;176(3):1469-83
pubmed: 20110411
Nature. 2018 Feb 22;554(7693):544-548
pubmed: 29443960
Front Mol Biosci. 2021 Feb 18;8:611508
pubmed: 33681290
Eur J Cancer. 2020 Jun;132:71-84
pubmed: 32334338
Eur J Immunol. 2002 Jan;32(1):193-202
pubmed: 11754360
JCI Insight. 2020 May 21;5(10):
pubmed: 32324594
Nat Commun. 2017 Apr 27;8:15095
pubmed: 28447602
Blood. 2008 Nov 1;112(9):3696-703
pubmed: 18698005
Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20212-7
pubmed: 24277834
Sci Rep. 2018 Jan 22;8(1):1323
pubmed: 29358632
Front Immunol. 2019 Apr 24;10:847
pubmed: 31068935
Cancer Res. 2009 Apr 1;69(7):3077-85
pubmed: 19293190
Cancer Immunol Res. 2017 Nov;5(11):978-991
pubmed: 29066497
Oncoimmunology. 2016 Oct 7;5(12):e1240859
pubmed: 28123878
Clin Cancer Res. 2020 Apr 15;26(8):1997-2010
pubmed: 31964786
Oncol Lett. 2021 Oct;22(4):696
pubmed: 34457051
CA Cancer J Clin. 2020 Jan;70(1):7-30
pubmed: 31912902
Immunity. 2021 May 11;54(5):859-874
pubmed: 33838745
Cancer Res. 2011 Dec 15;71(24):7463-70
pubmed: 22025564
J Clin Med. 2019 Nov 15;8(11):
pubmed: 31731701
Int J Oncol. 2016 May;48(5):2087-97
pubmed: 26983899
Nat Med. 2020 Jun;26(6):878-885
pubmed: 32451495
Cancers (Basel). 2021 Jun 15;13(12):
pubmed: 34203869
Breast Cancer Res. 2012 Feb 14;14(1):R30
pubmed: 22333315
Clin Cancer Res. 2020 Nov 15;26(22):6051-6063
pubmed: 32873571
Nat Commun. 2020 Apr 9;11(1):1749
pubmed: 32273499
J Immunol. 2009 Feb 1;182(3):1746-55
pubmed: 19155524
Cell Death Dis. 2020 Apr 16;11(4):234
pubmed: 32300100
Mol Immunol. 2007 Jul;44(13):3283-90
pubmed: 17403540
Cancer Discov. 2020 Feb;10(2):232-253
pubmed: 31699795
Cancers (Basel). 2021 Mar 15;13(6):
pubmed: 33803936
J Immunol. 2008 May 15;180(10):6713-24
pubmed: 18453591
Biomed Pharmacother. 2019 Mar;111:891-900
pubmed: 30841468
Cell Mol Gastroenterol Hepatol. 2021;12(1):41-58
pubmed: 33548597
Pancreatology. 2019 Mar;19(2):340-345
pubmed: 30685120
J Immunol. 2000 Sep 15;165(6):3423-9
pubmed: 10975862

Auteurs

Laia Gorchs (L)

Department of Laboratory Medicine, Karolinska Institutet, 141 52 Stockholm, Sweden.

Marlies Oosthoek (M)

Department of Laboratory Medicine, Karolinska Institutet, 141 52 Stockholm, Sweden.

Tülay Yucel-Lindberg (T)

Department of Dental Medicine, Karolinska Institutet, 141 52 Stockholm, Sweden.

Carlos Fernández Moro (CF)

Department of Laboratory Medicine, Karolinska Institutet, 141 52 Stockholm, Sweden.
Department of Pathology and Cancer Diagnostics, Karolinska University Hospital, 141 57 Stockholm, Sweden.

Helen Kaipe (H)

Department of Laboratory Medicine, Karolinska Institutet, 141 52 Stockholm, Sweden.
Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, 141 52 Stockholm, Sweden.

Classifications MeSH