{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T10:31:20Z","timestamp":1789900280055,"version":"4.0.1"},"reference-count":33,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2016,11,29]],"date-time":"2016-11-29T00:00:00Z","timestamp":1480377600000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["JP25460497"],"award-info":[{"award-number":["JP25460497"]}]},{"name":"JSPS KAKENHI","award":["JP25293089"],"award-info":[{"award-number":["JP25293089"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:p>Immune escape and tolerance in the tumor microenvironment are closely involved in tumor progression, and are caused by T\u2010cell exhaustion and mediated by the inhibitory signaling of immune checkpoint molecules including programmed death\u20101 (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101), cytotoxic T\u2010lymphocyte associated protein 4, and T\u2010cell immunoglobulin and mucin domaincontaining molecule\u20103. In the present study, we investigated the expression of the <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 ligand 1 (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1) in a lymphoma microenvironment using paraffin\u2010embedded tissue samples, and subsequently studied the detailed mechanism of upregulation of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1 on macrophages using cultured human macrophages and lymphoma cell lines. We found that macrophages in lymphoma tissues of almost all cases of adult T\u2010cell leukemia\/lymphoma (<jats:styled-content style=\"fixed-case\">ATLL<\/jats:styled-content>), follicular lymphoma and diffuse large B\u2010cell lymphoma expressed <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1. Cell culture studies showed that the conditioned medium of <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content>\u2010T and <jats:styled-content style=\"fixed-case\">SLVL<\/jats:styled-content> cell lines induced increased expression of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1\/2 on macrophages, and that this <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1\/2 overexpression was dependent on activation of signal transducer and activator of transcription 3 (Stat3). <jats:italic>In\u00a0vitro<\/jats:italic> studies including cytokine array analysis showed that <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201027 (heterodimer of p28 and <jats:styled-content style=\"fixed-case\">EBI<\/jats:styled-content>3) induced overexpression of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1\/2 on macrophages via Stat3 activation. Because lymphoma cell lines produced <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201027B (<jats:styled-content style=\"fixed-case\">EBI<\/jats:styled-content>3) but not <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201027p28, it was proposed that the <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201027p28 derived from macrophages and the <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201027B (<jats:styled-content style=\"fixed-case\">EBI<\/jats:styled-content>3) derived from lymphoma cells formed an <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201027 (heterodimer) that induced <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1\/2 overexpression. Although the significance of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1\/2 expressions on macrophages in lymphoma progression has never been clarified, an <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201027\u2010Stat3 axis might be a target for immunotherapy for lymphoma patients.<\/jats:p>","DOI":"10.1111\/cas.13065","type":"journal-article","created":{"date-parts":[[2016,8,26]],"date-time":"2016-08-26T14:19:39Z","timestamp":1472221179000},"page":"1696-1704","source":"Crossref","is-referenced-by-count":119,"title":["An IL\u201027\/Stat3 axis induces expression of programmed cell death 1 ligands (<scp>PD<\/scp>\u2010L1\/2) on infiltrating macrophages in lymphoma"],"prefix":"10.1111","volume":"107","author":[{"given":"Hasita","family":"Horlad","sequence":"first","affiliation":[{"name":"Department of Cell Pathology Graduate School of Medical Sciences Kumamoto University Kumamoto 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