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 |