Research Papers:

Changes in T-cell subpopulations and cytokine network during early period of ibrutinib therapy in chronic lymphocytic leukemia patients: the significant decrease in T regulatory cells number

Monika Podhorecka _, Aneta Goracy, Agnieszka Szymczyk, Malgorzata Kowal, Blanca Ibanez, Olga Jankowska-Lecka, Arkadiusz Macheta, Aleksandra Nowaczynska, Elzbieta Drab-Urbanek, Sylwia Chocholska, Dariusz Jawniak and Marek Hus

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Oncotarget. 2017; 8:34661-34669. https://doi.org/10.18632/oncotarget.16148

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Monika Podhorecka1, Aneta Goracy1, Agnieszka Szymczyk1, Malgorzata Kowal1, Blanca Ibanez1, Olga Jankowska-Lecka1, Arkadiusz Macheta1, Aleksandra Nowaczynska1, Elzbieta Drab-Urbanek1, Sylwia Chocholska1, Dariusz Jawniak1 and Marek Hus1

1Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland

Correspondence to:

Monika Podhorecka, email: [email protected]

Keywords: chronic lymphocytic leukemia, cytokines, ibrutinib, T-cells, T regulatory cells

Received: January 16, 2017    Accepted: February 08, 2017    Published: March 13, 2017


B cell receptor (BCR) stimulation signal plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), and kinase inhibitors directed toward the BCR pathway are now the promising anti-leukemic drugs. Ibrutinib, a Bruton tyrosine kinase inhibitor, demonstrates promising clinical activity in CLL. It is reported that ibrutinib, additionally to directly targeting leukemic cells, also inhibits the interactions of these cells with T cells, macrophages and accessory cells. Assessment of these mechanisms is important because of their non -direct anti-leukemic effects and to identify possible side effects connected with long-term drug administration.

The aim of this study was to assess the in vivo effects of ibrutinib on T-cell subpopulations and cytokine network in CLL. The analysis was performed on a group of 19 patients during first month of ibrutinib therapy. The standard multicolor flow cytometry and cytometric bead array methods were used for assessment of T-cell subsets and cytokines/chemokines, respectively.

The data obtained indicates that Ibrutinib treatment results in changes in T-cell subpopulations and cytokine network in CLL patients. Particularly, a significant reduction of T regulatory cells in peripheral blood was observed. By targeting these populations of T cells Ibrutinib can stimulate rejection of tumor cells by the immune system.

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