{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:19:20Z","timestamp":1790522360819,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,6,27]],"date-time":"2018-06-27T00:00:00Z","timestamp":1530057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["17ck0106287h0001"],"award-info":[{"award-number":["17ck0106287h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["16cm0106301h0001"],"award-info":[{"award-number":["16cm0106301h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["15ck0106132h0002"],"award-info":[{"award-number":["15ck0106132h0002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:p>Adult T\u2010cell leukemia\/lymphoma (<jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content>) is caused by Human T\u2010cell lymphotropic\/leukemia virus type 1 (<jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101), and a higher <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101 provirus load in <jats:styled-content style=\"fixed-case\">PBMC<\/jats:styled-content> is a risk factor for <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content> development. Here, we document a significant inverse correlation between the function of <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101 Tax\u2010specific <jats:styled-content style=\"fixed-case\">CTL<\/jats:styled-content> (Tax\u2010<jats:styled-content style=\"fixed-case\">CTL<\/jats:styled-content>), as assessed by ex\u00a0vivo cytokine production in response to cognate peptide, and the <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101 provirus load in <jats:styled-content style=\"fixed-case\">PBMC<\/jats:styled-content> in both <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101 asymptomatic carriers (<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>) (Spearman rank correlation coefficient [<jats:italic>R<\/jats:italic>s]\u00a0=\u00a0\u22120.494, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.037, n\u00a0=\u00a018) and <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content> patients (<jats:italic>R<\/jats:italic>s\u00a0=\u00a0\u22120.774, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.001, n\u00a0=\u00a015). There was also a significant correlation between the <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101 provirus load and the percentage of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101\u2010positive Tax\u2010<jats:styled-content style=\"fixed-case\">CTL<\/jats:styled-content> in both <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101 <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content> (<jats:italic>R<\/jats:italic>s\u00a0=\u00a00.574, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.013) and <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content> patients (<jats:italic>R<\/jats:italic>s\u00a0=\u00a00.676, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.006). Furthermore, the percentage of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101\u2010positive Tax\u2010<jats:styled-content style=\"fixed-case\">CTL<\/jats:styled-content> was inversely correlated with their function in <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101 <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content> (<jats:italic>R<\/jats:italic>s\u00a0=\u00a0\u22120.542, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.020), and <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content> patients (<jats:italic>R<\/jats:italic>s\u00a0=\u00a0\u22120.639, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.010). These findings indicate that the function of Tax\u2010<jats:styled-content style=\"fixed-case\">CTL<\/jats:styled-content> decreased as their programmed cell death protein 1 (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101) levels increased, parallel to the increased <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101 provirus load in <jats:styled-content style=\"fixed-case\">PBMC<\/jats:styled-content>. We propose that functional Tax\u2010<jats:styled-content style=\"fixed-case\">CTL<\/jats:styled-content> are crucial for determining the <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101 provirus load in <jats:styled-content style=\"fixed-case\">PBMC<\/jats:styled-content>, not only in <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101 <jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>, but also in <jats:styled-content style=\"fixed-case\">ATL<\/jats:styled-content>, and that <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 expression levels are reliable markers of Tax\u2010<jats:styled-content style=\"fixed-case\">CTL<\/jats:styled-content> function. Thus, modulating the immunological equilibrium between Tax\u2010<jats:styled-content style=\"fixed-case\">CTL<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101\u2010infected cells to achieve dominance of functional effectors could represent an ideal strategy for controlling <jats:styled-content style=\"fixed-case\">HTLV<\/jats:styled-content>\u20101\u2010associated disease.<\/jats:p>","DOI":"10.1111\/cas.13654","type":"journal-article","created":{"date-parts":[[2018,5,30]],"date-time":"2018-05-30T06:56:50Z","timestamp":1527663410000},"page":"2383-2390","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Human T\u2010cell lymphotropic\/leukemia virus type 1 (<scp>HTLV<\/scp>\u20101) Tax\u2010specific T\u2010cell exhaustion in <scp>HTLV<\/scp>\u20101\u2010infected individuals"],"prefix":"10.1111","volume":"109","author":[{"given":"Ayako","family":"Masaki","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology Nagoya City University Graduate School of Medical Sciences Nagoya Japan"},{"name":"Department of Anatomic Pathology and Molecular Diagnostics Nagoya City University Graduate School of Medical Sciences Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1060-0777","authenticated-orcid":false,"given":"Takashi","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Nagoya City University Graduate School of Medical Sciences Nagoya Japan"},{"name":"Division of Hematology and Oncology Department of Internal Medicine School of Medicine Iwate Medical University Morioka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Tumor Immunology Aichi Medical University School of Medicine Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asahi","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Nagoya City University Graduate School of Medical Sciences Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Narita","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Nagoya City University Graduate School of Medical Sciences Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiori","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Nagoya City University Graduate School of Medical Sciences Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9617-486X","authenticated-orcid":false,"given":"Masaki","family":"Ri","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Nagoya City University Graduate School of Medical Sciences Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Kusumoto","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Nagoya City University Graduate School of Medical Sciences Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Komatsu","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Nagoya City University Graduate School of Medical Sciences Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Inagaki","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology and Molecular Diagnostics Nagoya City University Graduate School of Medical Sciences Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuzo","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Tumor Immunology Aichi Medical University School of Medicine Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4951-960X","authenticated-orcid":false,"given":"Shinsuke","family":"Iida","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Nagoya City University Graduate School of Medical Sciences Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1991.tb08051.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70202-5"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2111"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-12-257410"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2012.02371.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202692"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301952"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-09-379982"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa4971"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3415"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.11.4243.bloodjournal86114243"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-2697"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.37.3472"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13338"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2035"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3862"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20011723"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02021-06"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.9.3094"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/9525"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13302"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1803181"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-03-414490"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2013.09.014"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.272"}],"container-title":["Cancer 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