論文 - 詳細
| RRC ID | 64570 |
|---|---|
| 著者 | Horlad H, Ma C, Yano H, Pan C, Ohnishi K, Fujiwara Y, Endo S, Kikukawa Y, Okuno Y, Matsuoka M, Takeya M, Komohara Y. |
| 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. |
| ジャーナル | Cancer Sci |
| 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. |
| 巻・号 | 107(11) |
| ページ | 1696-1704 |
| 公開日 | 2016-11-1 |
| DOI | 10.1111/cas.13065 |
| PMID | 27564404 |
| PMC | PMC5132271 |
| MeSH | B7-H1 Antigen / biosynthesis B7-H1 Antigen / genetics B7-H1 Antigen / metabolism* Cell Line, Tumor Culture Media, Conditioned / pharmacology Humans Interleukins / metabolism* Leukemia-Lymphoma, Adult T-Cell / immunology* Leukemia-Lymphoma, Adult T-Cell / metabolism* Macrophages / drug effects Macrophages / metabolism* Minor Histocompatibility Antigens / metabolism* Programmed Cell Death 1 Ligand 2 Protein / biosynthesis Programmed Cell Death 1 Ligand 2 Protein / genetics Programmed Cell Death 1 Ligand 2 Protein / metabolism* STAT3 Transcription Factor / metabolism* Up-Regulation / drug effects |
| IF | 4.966 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | SKW-3(RCB1168) MOLT-4(RCB0206) 103-LCL(RCB2082) 141-LCL(RCB2083) DAUDI(RCB1640) TL-1(RCB1871) SLVL(RCB1702) RAJI(RCB1647) NALM-6(RCB1933) BALL-1 |