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dc.contributor.author | Horlad, Hasita | en |
dc.contributor.author | Ma, Chaoya | en |
dc.contributor.author | Yano, Hiromu | en |
dc.contributor.author | Pan, Cheng | en |
dc.contributor.author | Ohnishi, Koji | en |
dc.contributor.author | Fujiwara, Yukio | en |
dc.contributor.author | Endo, Shinya | en |
dc.contributor.author | Kikukawa, Yoshitaka | en |
dc.contributor.author | Okuno, Yutaka | en |
dc.contributor.author | Matsuoka, Masao | en |
dc.contributor.author | Takeya, Motohiro | en |
dc.contributor.author | Komohara, Yoshihiro | en |
dc.contributor.alternative | 松岡, 雅雄 | ja |
dc.date.accessioned | 2017-04-19T04:11:43Z | - |
dc.date.available | 2017-04-19T04:11:43Z | - |
dc.date.issued | 2016-11 | - |
dc.identifier.issn | 1347-9032 | - |
dc.identifier.uri | http://hdl.handle.net/2433/219642 | - |
dc.description.abstract | Immune escape and tolerance in the tumor microenvironment are closely involved in tumor progression, and are caused by T-cell exhaustion and mediated by the inhibitory signaling of immune checkpoint molecules including programmed death-1 (PD-1), cytotoxic T-lymphocyte associated protein 4, and T-cell immunoglobulin and mucin domaincontaining molecule-3. In the present study, we investigated the expression of the PD-1 ligand 1 (PD-L1) in a lymphoma microenvironment using paraffin-embedded tissue samples, and subsequently studied the detailed mechanism of upregulation of PD-L1 on macrophages using cultured human macrophages and lymphoma cell lines. We found that macrophages in lymphoma tissues of almost all cases of adult T-cell leukemia/lymphoma (ATLL), follicular lymphoma and diffuse large B-cell lymphoma expressed PD-L1. Cell culture studies showed that the conditioned medium of ATL-T and SLVL cell lines induced increased expression of PD-L1/2 on macrophages, and that this PD-L1/2 overexpression was dependent on activation of signal transducer and activator of transcription 3 (Stat3). In vitro studies including cytokine array analysis showed that IL-27 (heterodimer of p28 and EBI3) induced overexpression of PD-L1/2 on macrophages via Stat3 activation. Because lymphoma cell lines produced IL-27B (EBI3) but not IL-27p28, it was proposed that the IL-27p28 derived from macrophages and the IL-27B (EBI3) derived from lymphoma cells formed an IL-27 (heterodimer) that induced PD-L1/2 overexpression. Although the significance of PD-L1/2 expressions on macrophages in lymphoma progression has never been clarified, an IL-27-Stat3 axis might be a target for immunotherapy for lymphoma patients. | en |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Wiley-Blackwell | en |
dc.rights | © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. | en |
dc.rights | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. | en |
dc.subject | CD163 | en |
dc.subject | macrophage | en |
dc.subject | PD-L1 | en |
dc.subject | PD-L2 | en |
dc.subject | tumor-associated macrophages | en |
dc.title | An IL-27/Stat3 axis induces expression of programmed cell death 1 ligands (PD-L1/2) on infiltrating macrophages in lymphoma | en |
dc.type | journal article | - |
dc.type.niitype | Journal Article | - |
dc.identifier.jtitle | Cancer Science | en |
dc.identifier.volume | 107 | - |
dc.identifier.issue | 11 | - |
dc.identifier.spage | 1696 | - |
dc.identifier.epage | 1704 | - |
dc.relation.doi | 10.1111/cas.13065 | - |
dc.textversion | publisher | - |
dc.identifier.pmid | 27564404 | - |
dcterms.accessRights | open access | - |
datacite.awardNumber | JP25460497 | - |
datacite.awardNumber | JP25293089 | - |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName.alternative | Japan Society for the Promotion of Science (JSPS) | en |
jpcoar.funderName.alternative | Japan Society for the Promotion of Science (JSPS) | en |
出現コレクション: | 学術雑誌掲載論文等 |
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