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Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia
University of Helsinki, Finland; Helsinki University Hospital, Finland.
Uppsala University Hospital, Sweden; Uppsala University, Sweden.
Karolinska Institute, Sweden.
CHU Poitiers, France.
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2017 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 5, p. 1108-1116Article in journal (Refereed) Published
Abstract [en]

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 naive CD56(bright) NK cells had decreased relapse-free survival. In addition, the TNF-alpha/IFN-gamma 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.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2017. Vol. 31, no 5, p. 1108-1116
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Hematology
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URN: urn:nbn:se:liu:diva-137599DOI: 10.1038/leu.2016.360ISI: 000400464800009PubMedID: 27890936OAI: oai:DiVA.org:liu-137599DiVA, id: diva2:1097371
Note

Funding Agencies|Nordic Cancer Union; Finnish Society of Hematology; Biomedicum Helsinki Foundation; Research Foundation of Blood Diseases in Finland; Academy of Finland; Finnish Cancer Organizations; Signe and Ane Gyllenberg Foundation; Finnish Cancer Institute; Doctoral Programme in Clinical Research in the University of Helsinki

Available from: 2017-05-22 Created: 2017-05-22 Last updated: 2018-04-18

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Lotfi, Kourosh

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Lotfi, KouroshDreimane, Arta
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Division of Drug ResearchFaculty of Medicine and Health SciencesDepartment of HaematologyDepartment of Clinical and Experimental Medicine
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