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タイトル: | An IL-27/Stat3 axis induces expression of programmed cell death 1 ligands (PD-L1/2) on infiltrating macrophages in lymphoma |
著者: | Horlad, Hasita Ma, Chaoya Yano, Hiromu Pan, Cheng Ohnishi, Koji Fujiwara, Yukio Endo, Shinya Kikukawa, Yoshitaka Okuno, Yutaka Matsuoka, Masao Takeya, Motohiro Komohara, Yoshihiro |
著者名の別形: | 松岡, 雅雄 |
キーワード: | CD163 macrophage PD-L1 PD-L2 tumor-associated macrophages |
発行日: | Nov-2016 |
出版者: | Wiley-Blackwell |
誌名: | Cancer Science |
巻: | 107 |
号: | 11 |
開始ページ: | 1696 |
終了ページ: | 1704 |
抄録: | 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. |
著作権等: | © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. 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. |
URI: | http://hdl.handle.net/2433/219642 |
DOI(出版社版): | 10.1111/cas.13065 |
PubMed ID: | 27564404 |
出現コレクション: | 学術雑誌掲載論文等 |

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