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
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