{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:16:36Z","timestamp":1790223396190,"version":"4.1.0"},"reference-count":47,"publisher":"American Society of Hematology","issue":"10","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,5,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Skin-related adverse events (AEs) occur frequently in adult T-cell leukemia-lymphoma (ATL) patients treated with mogamulizumab, a humanized anti-CCR4 monoclonal antibody. This study was undertaken to elucidate the mechanisms of mogamulizumab-induced skin-related AEs. We analyzed the T-cell receptor \u03b2 chain repertoire in ATL patients\u2019 peripheral blood mononuclear cells (PBMCs) before and after mogamulizumab. Skin-related AEs were present in 16 patients and were absent in 8 patients. Additionally, we included 11 patients before and after chemotherapy without mogamulizumab. Immune-related gene expression in PBMCs before and after mogamulizumab was also assessed (n = 24). Mogamulizumab treatment resulted in CCR4+ T-cell depletion, and the consequent lymphopenia provoked homeostatic CD8+ T-cell proliferation, as evidenced by increased expressions of CD8B and CD8A, which were significantly greater in patients with skin-related AEs than in those without them. We hypothesize that proliferation is driven by the engagement of self-antigens, including skin-related antigens, in the face of regulatory T-cell depletion. Together with the observed activated antigen presentation function, this resulted in T-cell diversification that was significantly greater in patients with skin-related AEs than in those without. We found that the CD8+ T cells that proliferated and diversified after mogamulizumab treatment were almost entirely newly emerged clones. There was an inverse relationship between the degree of CCR4+ T-cell depletion and increased CD8+ T-cell proliferation and diversification. Thus, lymphocyte-depleting mogamulizumab treatment provokes homeostatic CD8+ T-cell proliferation predominantly of newly emerging clones, some of which could have important roles in the pathogenesis of mogamulizumab-induced skin-related AEs.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020001641","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T18:29:14Z","timestamp":1589999354000},"page":"2180-2191","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":19,"title":["Robust CD8+ T-cell proliferation and diversification after mogamulizumab in patients with adult T-cell leukemia-lymphoma"],"prefix":"10.1182","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5384-3787","authenticated-orcid":false,"given":"Masato","family":"Saito","sequence":"first","affiliation":[{"name":"R&D Division, Kyowa Kirin Co. 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