Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia.
Mette Ilander,Ulla Olsson-Strömberg,Ulla Olsson-Strömberg,Heinrich Schlums,Joelle Guilhot,Oscar Brück,Hanna Lähteenmäki,Tiina Kasanen,Perttu Koskenvesa,Stina Söderlund,Martin Höglund,Berit Markevärn,Anders Själander,Kourosh Lotfi,Arta Dreimane,Anna Lübking,Elis Holm,Mats Björeman,Sören Lehmann,Sören Lehmann,Sören Lehmann,Leif Stenke,Lotta Ohm,Tobias Gedde-Dahl,Waleed Majeed,Hans Ehrencrona,S Koskela,Susanne Saussele,Mahon Fx,Kimmo Porkka,Henrik Hjorth-Hansen,Yenan T. Bryceson,Johan Richter,Satu Mustjoki +33 more
TLDR
The role of NK cells in sustaining remission is highlighted and the status of CML as an immunogenic tumor warranting novel clinical trials with immunomodulating agents is strengthened.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 naive 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.read more
Citations
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Control of Metastasis by NK Cells
TL;DR: The cancer-cell-intrinsic and -extrinsics factors that regulate metastasis are outlined, the key role of natural killer cells in the control of metastatic dissemination is discussed, and potential therapeutic approaches to prevent or target metastatic disease are presented.
Journal ArticleDOI
Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial
Susanne Saussele,Johan Richter,Joelle Guilhot,Franz Gruber,Henrik Hjorth-Hansen,Antonio Almeida,Jeroen Janssen,Jiri Mayer,Perttu Koskenvesa,Panayiotis Panayiotidis,Ulla Olsson-Strömberg,Joaquin Martinez-Lopez,Philippe Rousselot,Hanne Vestergaard,Hans Ehrencrona,Veli Kairisto,Katerina Machova Polakova,Martin Müller,Satu Mustjoki,Marc G. Berger,Alice Fabarius,Wolf-Karsten Hofmann,Andreas Hochhaus,Markus Pfirrmann,Francois-Xavier Mahon,Gert J. Ossenkoppele,Maria Pagoni,Stina Söderlund,Martine Escoffre-Barbe,Gabriel Etienne,Jolanta Dengler,Françoise Huguet,Nikolas von Bubnoff,Hana Klamova,Edgar Faber,François Guilhot,Kourosh Lotfi,Delphine Rea,Tim H. Brümmendorf,Gorgine E. de Greef,Leif Stenke,Franck E. Nicolini,Laurence Legros,Andreas Burchert,Jaroslava Voglová,Aude Charbonnier,Emmanuel Gyan,Volker Kunzmann,Peter E. Westerweel +48 more
TL;DR: In this paper, a prospective, non-randomised trial was conducted at 61 European centres in 11 countries to investigate the impact of stopping TKI therapy on the survival of patients with chronic myeloid leukaemia.
Journal Article
Adaptive Immune Features of Natural Killer Cells
TL;DR: In this paper, the authors used a mouse model of cytomegalovirus infection to show that, like T cells, NK cells bearing the virus-specific Ly49H receptor proliferate 100fold in the spleen and 1,000-fold in liver after infection.
Journal ArticleDOI
Chronic myeloid leukemia, version 2.2021
Michael W. Deininger,Neil P. Shah,Jessica K. Altman,Ellin Berman,Ravi Bhatia,Bhavana Bhatnagar,Daniel J. DeAngelo,Jason Gotlib,Gabriela S. Hobbs,Lori J. Maness,Monica Mead,Leland Metheny,Sanjay R. Mohan,Joseph O. Moore,Kiran Naqvi,Vivian G. Oehler,Arnel Pallera,Mrinal M. Patnaik,Keith W. Pratz,Iskra Pusic,Michal G. Rose,B. Douglas Smith,David S. Snyder,Kendra Sweet,Moshe Talpaz,James E. Thompson,David T. Yang,Kristina M. Gregory,Hema Sundar +28 more
TL;DR: Tyrosine kinase inhibitor therapy is a highly effective first-line treatment option for all patients with newly diagnosed chronic phase CML.
Journal ArticleDOI
De-escalation of tyrosine kinase inhibitor therapy before complete treatment discontinuation in patients with chronic myeloid leukaemia (DESTINY): a non-randomised, phase 2 trial
Richard E. Clark,Fotios Polydoros,Jane F. Apperley,Dragana Milojkovic,Katherine Rothwell,Christopher Pocock,Jennifer Byrne,Hugues de Lavallade,Wendy Osborne,L. G. Robinson,Stephen G. O'Brien,Lucy Read,Letizia Foroni,Mhairi Copland +13 more
TL;DR: Initial de-escalation before discontinuation might improve the success of TFR protocols, although the mechanism of its benefit is not yet clear and the findings suggest that TFR merits further study in patients with stable MMR.
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