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Article: Inhibition of TGF-B signaling in combination with TLR7 ligation re-programs a tumoricidal phenotype in tumor-associated macrophages

TitleInhibition of TGF-B signaling in combination with TLR7 ligation re-programs a tumoricidal phenotype in tumor-associated macrophages
Authors
KeywordsFunctional re-programming
TGF-β
TLR7
Tumor-associated macrophages
TLR4
Issue Date2013
PublisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canlet
Citation
Cancer Letters, 2013, v. 331 n. 2, p. 239-249 How to Cite?
AbstractInadequate immunity that occurs in a tumor environment is in part due to the presence of M2-type tumor-associated macrophages (TAMs). TGF-beta has a multi-functional role in tumor development including modulating the biological activity of both the tumor and TAMs. In this study, using an in vitro TAM/tumor cell co-culture system ligation of TLR7, which is expressed on TAMs but not the tumor cells, in the presence of TGF-beta receptor I inhibitor re-programmed the phenotype of the TAMs. In part they adopted the phenotype characteristic of M1-type macrophages, namely they had increased tumoricidal activity and elevated expression of iNOS, CD80 and MHC class II, while TGF-beta secretion was reduced. The reprogrammed phenotype was accompanied by enhanced NF-kappaB nuclear translocation. The pro-angiogenesis factor VEGF was down-regulated and in vivo the number of CD31-positive tumor capillaries was also reduced. Furthermore, in vivo we observed that TLR7 ligation/TGF-beta receptor I inhibition increased tumor apoptosis and elevated the number of CD4+, CD8+, and CD19+ cells as well as neutrophils infiltrating the tumor. Our data demonstrate that selective TLR stimulation with TGF-beta inhibition can reprogram TAMs towards an M1-like phenotype and thereby provides new perspectives in cancer therapy.
Persistent Identifierhttp://hdl.handle.net/10722/183691
ISSN
2015 Impact Factor: 5.992
2015 SCImago Journal Rankings: 2.331
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorPeng, Jen_US
dc.contributor.authorTsang, JYSen_US
dc.contributor.authorLi, Den_US
dc.contributor.authorNiu, Nen_US
dc.contributor.authorHo, DHHen_US
dc.contributor.authorLau, KFen_US
dc.contributor.authorLui, VCHen_US
dc.contributor.authorLamb, JRen_US
dc.contributor.authorChen, Yen_US
dc.contributor.authorTam, PKHen_US
dc.date.accessioned2013-06-18T04:08:24Z-
dc.date.available2013-06-18T04:08:24Z-
dc.date.issued2013en_US
dc.identifier.citationCancer Letters, 2013, v. 331 n. 2, p. 239-249en_US
dc.identifier.issn0304-3835-
dc.identifier.urihttp://hdl.handle.net/10722/183691-
dc.description.abstractInadequate immunity that occurs in a tumor environment is in part due to the presence of M2-type tumor-associated macrophages (TAMs). TGF-beta has a multi-functional role in tumor development including modulating the biological activity of both the tumor and TAMs. In this study, using an in vitro TAM/tumor cell co-culture system ligation of TLR7, which is expressed on TAMs but not the tumor cells, in the presence of TGF-beta receptor I inhibitor re-programmed the phenotype of the TAMs. In part they adopted the phenotype characteristic of M1-type macrophages, namely they had increased tumoricidal activity and elevated expression of iNOS, CD80 and MHC class II, while TGF-beta secretion was reduced. The reprogrammed phenotype was accompanied by enhanced NF-kappaB nuclear translocation. The pro-angiogenesis factor VEGF was down-regulated and in vivo the number of CD31-positive tumor capillaries was also reduced. Furthermore, in vivo we observed that TLR7 ligation/TGF-beta receptor I inhibition increased tumor apoptosis and elevated the number of CD4+, CD8+, and CD19+ cells as well as neutrophils infiltrating the tumor. Our data demonstrate that selective TLR stimulation with TGF-beta inhibition can reprogram TAMs towards an M1-like phenotype and thereby provides new perspectives in cancer therapy.-
dc.languageengen_US
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canlet-
dc.relation.ispartofCancer Lettersen_US
dc.rightsNOTICE: this is the author’s version of a work that was accepted for publication in Cancer Letters. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Cancer Letters, 2013, v. 331 n. 2, p. 239-249. DOI: 10.1016/j.canlet.2013.01.001-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectFunctional re-programming-
dc.subjectTGF-β-
dc.subjectTLR7-
dc.subjectTumor-associated macrophages-
dc.subjectTLR4-
dc.subject.meshMacrophages - immunology-
dc.subject.meshNeoplasms, Experimental - blood supply - immunology - pathology-
dc.subject.meshSignal Transduction-
dc.subject.meshToll-Like Receptor 7 - metabolism-
dc.subject.meshTransforming Growth Factor beta - biosynthesis - metabolism-
dc.titleInhibition of TGF-B signaling in combination with TLR7 ligation re-programs a tumoricidal phenotype in tumor-associated macrophagesen_US
dc.typeArticleen_US
dc.identifier.emailTsang, JYS: jystsang@hku.hken_US
dc.identifier.emailHo, DHH: boderek@hku.hken_US
dc.identifier.emailLui, VCH: vchlui@hku.hken_US
dc.identifier.emailChen, Y: ychenc@hku.hken_US
dc.identifier.emailTam, PKH: paultam@hku.hken_US
dc.identifier.authorityLui, VCH=rp00363en_US
dc.identifier.authorityChen, Y=rp01318en_US
dc.identifier.authorityTam, PKH=rp00060en_US
dc.description.naturepostprint-
dc.identifier.doi10.1016/j.canlet.2013.01.001-
dc.identifier.pmid23318200-
dc.identifier.scopuseid_2-s2.0-84875364025-
dc.identifier.hkuros214475en_US
dc.identifier.volume331en_US
dc.identifier.issue2en_US
dc.identifier.spage239en_US
dc.identifier.epage249en_US
dc.identifier.isiWOS:000317801200014-
dc.publisher.placeIreland-

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