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An IL-27/Stat3 axis induces expression of programmed cell death 1 ligands ( PD-L1/2) on infiltrating macrophages in lymphoma.
- Source :
- Cancer Science; Nov2016, Vol. 107 Issue 11, p1696-1704, 9p
- Publication Year :
- 2016
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 13479032
- Volume :
- 107
- Issue :
- 11
- Database :
- Complementary Index
- Journal :
- Cancer Science
- Publication Type :
- Academic Journal
- Accession number :
- 119806565
- Full Text :
- https://doi.org/10.1111/cas.13065