Pirfenidone reduces immune-suppressive capacity of cancer-associated fibroblasts through targeting CCL17 and TNF-beta.

ABOULKHEYR ESTARABADI, H; Zhand, S; Thiery, JP; Warkiani, ME

Pirfenidone reduces immune-suppressive capacity of cancer-associated fibroblasts through targeting CCL17 and TNF-beta.

ABOULKHEYR ESTARABADI, H Zhand, S Thiery, JP Warkiani, ME

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Publisher:: OXFORD UNIV PRESS
Publication Type:: Journal Article
Citation:: Integrative biology : quantitative biosciences from nano to macro, 2020, 12, (7), pp. 188-197
Issue Date:: 2020-07

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Field	Value	Language
dc.contributor.author	ABOULKHEYR ESTARABADI, H
dc.contributor.author	Zhand, S
dc.contributor.author	Thiery, JP
dc.contributor.author	Warkiani, ME
dc.date.accessioned	2021-03-20T03:10:40Z
dc.date.available	2020-06-15
dc.date.available	2021-03-20T03:10:40Z
dc.date.issued	2020-07
dc.identifier.citation	Integrative biology : quantitative biosciences from nano to macro, 2020, 12, (7), pp. 188-197
dc.identifier.issn	1757-9694
dc.identifier.issn	1757-9708
dc.identifier.uri	http://hdl.handle.net/10453/147395
dc.description.abstract	Various factors in the tumor microenvironment (TME) regulate the expression of PD-L1 in carcinoma cells. The cancer-associated fibroblasts (CAFs) play a crucial role in regulating and rewiring TME to enhance their immune suppressive function and to favor the invasion of the malignant cells. Tumor progression may be retarded by targeting CAFs in the TME. Various studies highlighted the ability of targeting CAF with pirfenidone (PFD), leading to increased efficacy of chemotherapy. However, its potential for the reduction of immune-suppression capacity of CAFs remains to be elusive. Here, we assessed the effect of PFD on the expression of PD-L1 on CAF cells. Besides migration inhibitory effects of PFD on CAFs, the expression level of PD-L1 reduced in CAFs after treatment with PFD. The downstream analysis of released cytokines from CAFs showed that PFD significantly dropped the secretion of CCL17 and TNF-β, where a positive association between PFD-targeted proteins and PD-L1 was observed. These data suggest that the treatment of CAF within TME through the PFD may reduce the acquisition of CAF-mediated invasive and immune-suppressive capacity of breast carcinoma cells.
dc.format	Print
dc.language	eng
dc.publisher	OXFORD UNIV PRESS
dc.relation	http://purl.org/au-research/grants/nhmrc/1143377
dc.relation.ispartof	Integrative biology : quantitative biosciences from nano to macro
dc.relation.isbasedon	10.1093/intbio/zyaa014
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	0304 Medicinal and Biomolecular Chemistry, 0601 Biochemistry and Cell Biology, 1115 Pharmacology and Pharmaceutical Sciences
dc.subject.classification	General Science & Technology
dc.title	Pirfenidone reduces immune-suppressive capacity of cancer-associated fibroblasts through targeting CCL17 and TNF-beta.
dc.type	Journal Article
utslib.citation.volume	12
utslib.location.activity	England
utslib.for	0304 Medicinal and Biomolecular Chemistry
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	1115 Pharmacology and Pharmaceutical Sciences
utslib.for	0304 Medicinal and Biomolecular Chemistry
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	1115 Pharmacology and Pharmaceutical Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices
utslib.copyright.status	closed_access	*
pubs.consider-herdc	false
dc.date.updated	2021-03-20T03:10:37Z
pubs.issue	7
pubs.publication-status	Published
pubs.volume	12
utslib.citation.issue	7

Abstract:

Various factors in the tumor microenvironment (TME) regulate the expression of PD-L1 in carcinoma cells. The cancer-associated fibroblasts (CAFs) play a crucial role in regulating and rewiring TME to enhance their immune suppressive function and to favor the invasion of the malignant cells. Tumor progression may be retarded by targeting CAFs in the TME. Various studies highlighted the ability of targeting CAF with pirfenidone (PFD), leading to increased efficacy of chemotherapy. However, its potential for the reduction of immune-suppression capacity of CAFs remains to be elusive. Here, we assessed the effect of PFD on the expression of PD-L1 on CAF cells. Besides migration inhibitory effects of PFD on CAFs, the expression level of PD-L1 reduced in CAFs after treatment with PFD. The downstream analysis of released cytokines from CAFs showed that PFD significantly dropped the secretion of CCL17 and TNF-β, where a positive association between PFD-targeted proteins and PD-L1 was observed. These data suggest that the treatment of CAF within TME through the PFD may reduce the acquisition of CAF-mediated invasive and immune-suppressive capacity of breast carcinoma cells.

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http://hdl.handle.net/10453/147395