{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T23:43:30Z","timestamp":1792280610251,"version":"4.4.0"},"reference-count":37,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol Myers Squibb","doi-asserted-by":"publisher","award":["CA180-712"],"award-info":[{"award-number":["CA180-712"]}],"id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We prospectively evaluated whether cytotoxic T-lymphocyte (CTL) activation and T-cell receptor (TCR) V\u03b2 clonality predict treatment-free remission (TFR) after tyrosine kinase inhibitor (TKI) cessation in chronic-phase chronic myeloid leukemia (CML). Forty-five patients with sustained deep molecular response (DMR) were enrolled (On-TKI, n = 38; Off-TKI, n = 7) and underwent one-year immuno-monitoring from consent. The primary endpoint was 12-month TFR, defined as retention of MR4. Overall, 32\/45 patients (71%) maintained TFR at 12 months. Longer TKI exposure and stable DMR were associated with TFR; notably, patients fulfilling \u201c\u22657 years of TKI plus \u22651 year of DMR\u201d and exhibiting CTL activation features\u2014CD8 &gt; CD4, memory &gt; effector, and\/or highly activated CTL clones on TCR V\u03b2 repertoire\u2014showed the highest likelihood of durable TFR. By contrast, NK cells, effector Tregs, and G-\/M-MDSCs did not discriminate TFR status in this cohort. Although antigen specificity against CML stem cells was not directly tested, the memory-dominant CTL phenotype is consistent with immune control after antigen reduction. These findings suggest that a simple, clinically accessible strategy based on flow cytometric CTL profiling and TCR V\u03b2 clonality may help inform TKI discontinuation decisions in CML. External validation is warranted to confirm transportability and refine clinical thresholds.<\/jats:p>","DOI":"10.3390\/ijms27062713","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T09:35:57Z","timestamp":1773740157000},"page":"2713","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Activated Memory Cytotoxic T-Lymphocytes and T-Cell Receptor V\u03b2 Clonality Predict Treatment-Free Remission After Tyrosine Kinase Inhibitor Discontinuation in Chronic-Phase Chronic Myeloid Leukemia: A 1-Year Prospective Immuno-Monitoring Study"],"prefix":"10.3390","volume":"27","author":[{"given":"Tatsuro","family":"Jo","sequence":"first","affiliation":[{"name":"Department of Hematology, Japanese Red Cross Nagasaki Genbaku Hospital, Mori-machi 3-15, Nagasaki City 852-8511, Nagasaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Saburi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oita Prefectural Hospital, Toyo 2-8-1, Oita City 870-8511, Oita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9952-022X","authenticated-orcid":false,"given":"Taro","family":"Masunari","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Chugoku Central Hospital, Miyukicho Oazakamiiwanari 148-13, Fukuyama City 720-0001, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Noguchi","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Japanese Red Cross Nagasaki Genbaku Hospital, Mori-machi 3-15, Nagasaki City 852-8511, 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, Mori-machi 3-15, Nagasaki City 852-8511, Nagasaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Taguchi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Japanese Red Cross Nagasaki Genbaku Hospital, Mori-machi 3-15, Nagasaki City 852-8511, Nagasaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiichi","family":"Ohtsuka","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oita Prefectural Hospital, Toyo 2-8-1, Oita City 870-8511, Oita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuo","family":"Sezaki","sequence":"additional","affiliation":[{"name":"Department of Hematology, Chugoku Central Hospital, Miyukicho Oazakamiiwanari 148-13, Fukuyama City 720-0001, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0623-038X","authenticated-orcid":false,"given":"Ritsuko","family":"Kubota-Koketsu","sequence":"additional","affiliation":[{"name":"Specimen Analysis Team, Human Resource Development Division, Center for Infectious Disease Education and Research, The University of Osaka, Yamadaoka 2-2, Suita City 565-0871, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Kiguchi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Chugoku Central Hospital, Miyukicho Oazakamiiwanari 148-13, Fukuyama City 720-0001, Hiroshima, Japan"},{"name":"Division of Diabetes, Endocrinology and Hematology, Saitama Medical Center, Dokkyo Medical University, Minamikoshigaya 2-1-50, Koshigaya City 343-8555, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/s41375-020-0776-2","article-title":"European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia","volume":"34","author":"Hochhaus","year":"2020","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/S1470-2045(10)70233-3","article-title":"Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: The prospective, multicentre Stop Imatinib (STIM) trial","volume":"11","author":"Mahon","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1182\/blood-2013-02-483750","article-title":"Safety and efficacy of imatinib cessation for CML patients with stable 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