Changes in Both CD4+CD25+Foxp3+ Regulatory T Cells and CD3-CD56+ NK Cells in Patients with Chronic Myeloid Leukemia Treated with a Tyrosine Kinase Inhibitor

• Published in: Blood 2018-11, Vol.132 (Supplement 1), p.5424-5424
• Main Authors: Tajima, Fumihito, Adachi, Koji, Kawatani, Toshio, Nishio, Takaya, Suzumiya, Junji
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-99-112717

Background: The immunological graft-versus-leukemia effects associated with chronic myeloid leukemia (CML) are well-established. Both regulatory T cells (Treg) and natural killer (NK) cells play a role in the maintenance of CML. In this study, we examined changes in the number of circulating Treg and NK cells and the NK activity in CML patients before and after treatment with a tyrosine kinase inhibitor (TKI). Our goal was to evaluate the clinical significance of this treatment on these two different cell types. Moreover, the levels of these cells suggest that there is a need to make the TKI more effective as an immunotherapy. Patients and Methods: Treg and NK cells were characterized and quantified by flow cytometry in 27 newly diagnosed CML patients, 19 newly diagnosed patients with other myeloproliferative neoplasms (MPN), and 15 healthy controls (HC-group). CML patients, who were diagnosed as chronic phase and initially treated with a TKI between September 2007 and July 2017 and were followed up for more than 12 months were enrolled in the study. The molecular response was analyzed by quantitative PCR of the BCR-ABL fusion genes at approximately 6-month intervals after the initiation of treatment. After obtaining informed consent, peripheral blood (PB) was drawn from all patients at their initial diagnosis and at 6-month intervals thereafter. CD4+CD25+Foxp3+ Treg cells, CD3+CD4+T cells, CD3+CD8+ T cells, and CD3-CD56+ NK cells were analyzed using flow cytometry, and the absolute numbers of these cells were calculated. The NK activity was measured by the standard 51Cr release assay at an effector:target (E:T) ratio of 20:1. Results: The median age for CML patients was 65 years (range: 44-85), and 17 out of 27 of the patients were male. The median period of observation was 656 days. After 12 months, 12 CML patients (MMR-group) had a major molecular response (MMR), and 15 patients (NR-group) did not have a MMR. Treg% values in the PB before treatment in the CML-group (0.39±0.30%) were significantly lower than that in the HC-group (0.70±0.29%, p