{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:07:46Z","timestamp":1788847666509,"version":"build-2803163510"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Adult T-cell leukemia\/lymphoma (ATLL) is an aggressive HTLV-1-associated T-cell neoplasm, and durable control of relapsed\/refractory disease remains difficult without allogeneic hematopoietic stem cell transplantation. Mogamulizumab, an afucosylated anti-C-C chemokine receptor type 4 (CCR4) monoclonal antibody, and tucidinostat, an oral histone deacetylase inhibitor, have activity in this setting, but the immunovirological consequences of sequential CCR4-directed therapy and epigenetic modulation are unclear. We describe two patients with relapsed or refractory ATLL who achieved prolonged disease control after mogamulizumab\/tucidinostat-based sequential therapy and underwent longitudinal monitoring of Tax301\u2013309-specific CD8+ T cells, CD4\/CD8 dynamics, HTLV-1 proviral DNA, and T-cell receptor (TCR) V\u03b2 repertoire. Patient 1 had lymphoma-type ATLL with metabolic partial response after mogamulizumab plus EPOCH; tucidinostat was initiated 63 days after the final mogamulizumab dose. Tax301\u2013309-specific CD8+ T cells increased from 0.03% at tucidinostat initiation to &amp;gt;0.8% during long-term follow-up, and disease control persisted for 32 months after tucidinostat initiation. Patient 2 had multiply relapsed ATLL and received four cycles of sequential mogamulizumab\/tucidinostat, followed by rapid disappearance of circulating ATLL cells, normalization of soluble interleukin-2 receptor, and marked reduction of HTLV-1 proviral load from 565.7 copies\/1,000 peripheral blood mononuclear cells to low levels. Disease control persisted for 17 months after treatment discontinuation. In both patients, TCR V\u03b2 repertoire analysis showed memory CD8+ T-cell-predominant patterns, including expansion of a V\u03b22 memory CD8+ T-cell population. These observations are hypothesis-generating and suggest that sequential tumor debulking, CCR4\/Treg-axis modulation, and epigenetic treatment may create a context permissive for HTLV-1 antigen-specific cellular immune surveillance in selected patients with ATLL.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1919613","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:34:42Z","timestamp":1788845682000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Durable immunovirological control after sequential mogamulizumab and tucidinostat in relapsed or refractory adult T-cell leukemia\/lymphoma"],"prefix":"10.3389","volume":"17","author":[{"given":"Tatsuro","family":"Jo","sequence":"first","affiliation":[{"name":"Department of Hematology, Japanese Red Cross Nagasaki Genbaku Hospital","place":["Nagasaki City, Nagasaki, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Noguchi","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Japanese Red Cross Nagasaki Genbaku Hospital","place":["Nagasaki City, Nagasaki, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Japanese Red Cross Nagasaki Genbaku Hospital","place":["Nagasaki City, Nagasaki, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaho","family":"Umemoto","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Japanese Red Cross Nagasaki Genbaku Hospital","place":["Nagasaki City, Nagasaki, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Japanese Red Cross Nagasaki Genbaku Hospital","place":["Nagasaki City, Nagasaki, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saori","family":"Ikegami","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Japanese Red Cross Nagasaki Genbaku Hospital","place":["Nagasaki City, Nagasaki, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rena","family":"Baba","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Japanese Red Cross Nagasaki Genbaku Hospital","place":["Nagasaki City, Nagasaki, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoya","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Japanese Red Cross Nagasaki Genbaku Hospital","place":["Nagasaki City, Nagasaki, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadaharu","family":"Irie","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Japanese Red Cross Nagasaki Genbaku Hospital","place":["Nagasaki City, Nagasaki, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Department of Hematology, Japanese Red Cross Nagasaki Genbaku Hospital","place":["Nagasaki City, Nagasaki, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Sawayama","sequence":"additional","affiliation":[{"name":"Department of Hematology, Japanese Red Cross Nagasaki Genbaku Hospital","place":["Nagasaki City, Nagasaki, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Taguchi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Japanese Red Cross Nagasaki Genbaku Hospital","place":["Nagasaki City, Nagasaki, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuniko","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Pathology, Japanese Red Cross Nagasaki Genbaku Hospital","place":["Nagasaki City, Nagasaki, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuto","family":"Shigematsu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Japanese Red Cross Nagasaki Genbaku Hospital","place":["Nagasaki City, Nagasaki, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Department of Hematology, Japanese Red Cross Nagasaki Genbaku Hospital","place":["Nagasaki City, Nagasaki, Japan"]},{"name":"Department of Hematology, Nagasaki University Hospital, Nagasaki City","place":["Nagasaki, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1991.tb08051.x","article-title":"Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. 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