Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia

• Verfasst von: Ilander, Mette Matilda [VerfasserIn]
• Verfasst von: Saußele, Susanne [VerfasserIn]
• Titel: Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia
• Verf.angabe: M. Ilander, U. Olsson-Strömberg, H. Schlums, J. Guilhot, O. Brück, H. Lähteenmäki, T. Kasanen, P. Koskenvesa, S. Söderlund, M. Höglund, B. Markevärn, A. Själander, K. Lotfi, A. Dreimane, A. Lübking, E. Holm, M. Björeman, S. Lehmann, L. Stenke, L. Ohm, T. Gedde-Dahl, W. Majeed, H. Ehrencrona, S. Koskela, S. Saussele, F.-X. Mahon, K. Porkka, H. Hjorth-Hansen, Y. T. Bryceson, J. Richter, S. Mustjoki
• Jahr: 2017
• Umfang: 9 S.
• Fussnoten: Published: 28 November 2016 ; Gesehen am 05.11.2018
• Titel Quelle: Enthalten in: Leukemia
• Ort Quelle: London : Springer Nature, 1997
• Jahr Quelle: 2017
• Band/Heft Quelle: 31(2017), 5, Seite 1108-1116
• ISSN Quelle: 1476-5551
• DOI: doi:10.1038/leu.2016.360
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1582534322

Abstract

Recent studies suggest that a proportion of chronic myeloid leukemia (CML) patients in deep molecular remission can discontinue the tyrosine kinase inhibitor (TKI) treatment without disease relapse. In this multi-center, prospective clinical trial (EURO-SKI, NCT01596114) we analyzed the function and phenotype of T and NK cells and their relation to successful TKI cessation. Lymphocyte subclasses were measured from 100 imatinib-treated patients at baseline and 1 month after the discontinuation, and functional characterization of NK and T cells was done from 45 patients. The proportion of NK cells was associated with the molecular relapse-free survival as patients with higher than median NK-cell percentage at the time of drug discontinuation had better probability to stay in remission. Similar association was not found with T or B cells or their subsets. In non-relapsing patients the NK-cell phenotype was mature, whereas patients with more naïve CD56bright NK cells had decreased relapse-free survival. In addition, the TNF-α/IFN-γ cytokine secretion by NK cells correlated with the successful drug discontinuation. Our results highlight the role of NK cells in sustaining remission and strengthen the status of CML as an immunogenic tumor warranting novel clinical trials with immunomodulating agents.