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Article: Adiponectin receptor signaling on dendritic cells blunts antitumor immunity

TitleAdiponectin receptor signaling on dendritic cells blunts antitumor immunity
Authors
Issue Date2014
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2014, v. 74 n. 20, p. 5711-5722 How to Cite?
AbstractImmune escape is a fundamental trait of cancer. Dendritic cells (DC) that interact with T cells represent a crucial site for the development of tolerance to tumor antigens, but there remains incomplete knowledge about how DC-tolerizing signals evolve during tumorigenesis. In this study, we show that DCs isolated from patients with metastatic or locally advanced breast cancer express high levels of the adiponectin receptors AdipoR1 and AdipoR2, which are sufficient to blunt antitumor immunity. Mechanistic investigations of ligand-receptor interactions on DCs revealed novel signaling pathways for each receptor. AdipoR1 stimulated IL10 production by activating the AMPK and MAPKp38 pathways, whereas AdipoR2 modified inflammatory processes by activating the COX-2 and PPARγ pathways. Stimulation of these pathways was sufficient to block activation of NF-κB in DC, thereby attenuating their ability to stimulate antigen-specific T-cell responses. Together, our findings reveal novel insights into how DC-tolerizing signals evolve in cancer to promote immune escape. Furthermore, by defining a critical role for adiponectin signaling in this process, our work suggests new and broadly applicable strategies for immunometabolic therapy in patients with cancer.
Persistent Identifierhttp://hdl.handle.net/10722/210982
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorTan, PH-
dc.contributor.authorTyrrell, HEJ-
dc.contributor.authorGao, L-
dc.contributor.authorXu, D-
dc.contributor.authorQuan, J-
dc.contributor.authorGill, D-
dc.contributor.authorRai, L-
dc.contributor.authorDing, Y-
dc.contributor.authorPlant, G-
dc.contributor.authorChen, Y-
dc.contributor.authorXue, JZ-
dc.contributor.authorHanda, AI-
dc.contributor.authorGreenall, MJ-
dc.contributor.authorWalsh, K-
dc.contributor.authorXue, SA-
dc.date.accessioned2015-06-23T06:02:20Z-
dc.date.available2015-06-23T06:02:20Z-
dc.date.issued2014-
dc.identifier.citationCancer Research, 2014, v. 74 n. 20, p. 5711-5722-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/210982-
dc.description.abstractImmune escape is a fundamental trait of cancer. Dendritic cells (DC) that interact with T cells represent a crucial site for the development of tolerance to tumor antigens, but there remains incomplete knowledge about how DC-tolerizing signals evolve during tumorigenesis. In this study, we show that DCs isolated from patients with metastatic or locally advanced breast cancer express high levels of the adiponectin receptors AdipoR1 and AdipoR2, which are sufficient to blunt antitumor immunity. Mechanistic investigations of ligand-receptor interactions on DCs revealed novel signaling pathways for each receptor. AdipoR1 stimulated IL10 production by activating the AMPK and MAPKp38 pathways, whereas AdipoR2 modified inflammatory processes by activating the COX-2 and PPARγ pathways. Stimulation of these pathways was sufficient to block activation of NF-κB in DC, thereby attenuating their ability to stimulate antigen-specific T-cell responses. Together, our findings reveal novel insights into how DC-tolerizing signals evolve in cancer to promote immune escape. Furthermore, by defining a critical role for adiponectin signaling in this process, our work suggests new and broadly applicable strategies for immunometabolic therapy in patients with cancer.-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/-
dc.relation.ispartofCancer Research-
dc.titleAdiponectin receptor signaling on dendritic cells blunts antitumor immunity-
dc.typeArticle-
dc.identifier.emailQuan, J: chao.quan@hku.hk-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/0008-5472.CAN-13-1397-
dc.identifier.pmid25261236-
dc.identifier.pmcidPMC4314963-
dc.identifier.hkuros243602-
dc.identifier.volume74-
dc.identifier.issue20-
dc.identifier.spage5711-
dc.identifier.epage5722-
dc.publisher.placeUnited States-

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