{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T15:25:28Z","timestamp":1788881128181,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Adult T\u2010cell leukemia\/lymphoma (ATLL) is a relatively refractory peripheral T\u2010cell lymphoma caused by human T\u2010cell lymphotropic virus type 1 (HTLV\u20101). The objective of this study was to investigate the characteristics of long\u2010term survivors with ATLL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted an observational study of 75 aggressive\u2010type ATLL patients. Flow cytometry was conducted to analyze HTLV\u20101 Tax\u2010specific cytotoxic T\u2010lymphocytes (CTLs) and T\u2010cell receptor V\u03b2 gene repertoire.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We first evaluated six long\u2010term survivors among 37 patients who were newly diagnosed with ATLL and then treated with intensive chemotherapy without mogamulizumab, a monoclonal antibody for C\u2010C chemokine receptor four antigen. Reversal of the CD4\u2010to\u2010CD8 ratio (CD4\/CD8) in peripheral mononuclear cells was observed in all six patients. Three of these six patients showed reversed CD4\/CD8 immediately after herpes virus infection. Four of these six patients who could be examined demonstrated long\u2010term maintenance of HTLV\u20101 Tax\u2010specific CTLs. We subsequently identified four long\u2010term survivors among 38 patients who were newly diagnosed with ATLL and then treated with intensive chemotherapy plus mogamulizumab. All four patients showed reversed CD4\/CD8, and three of the four patients contracted herpes virus infection during immunochemotherapy. Six of the total 10 patients were subjected to CTL analyses. Tax\u2010specific CTLs were observed, and the CTLs that were almost entirely composed of memory CTLs in all patients were recorded. HTLV\u20101 provirus was also detected in all six patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data suggest that Tax\u2010specific memory CTLs probably, together with anticancer agents, eradicate ATLL cells and exhibit long\u2010term preventive effects from relapse ATLL. Thus, the strong activation of cellular immunity, such as herpes virus infection, seems to be necessary to induce such a potent number of Tax\u2010specific CTLs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.4689","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T11:48:52Z","timestamp":1647949732000},"page":"3238-3250","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp>HTLV<\/scp>\u20101 Tax\u2010specific memory cytotoxic T lymphocytes in long\u2010term survivors of aggressive\u2010type adult T\u2010cell leukemia\/lymphoma"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5415-6228","authenticated-orcid":false,"given":"Tatsuro","family":"Jo","sequence":"first","affiliation":[{"name":"Department of Hematology Japanese Red Cross Nagasaki Genbaku Hospital  Nagasaki 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