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
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
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DOI：
10.18632/oncotarget.16148
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发表时间：
2017-05-23
期刊：
影响因子：
--
通讯作者：
Hus, Marek
中科院分区：
文献类型：
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作者：
Podhorecka, Monika;Goracy, Aneta;Hus, Marek
B细胞受体(BCR)刺激信号在慢性淋巴细胞白血病(CLL)的发病机制中起着重要作用，针对BCR途径的激酶抑制剂是目前最有前途的抗白血病药物。Ibrutinib是一种Bruton酪氨酸激酶抑制剂，在慢性淋巴细胞性白血病中显示出良好的临床活性。据报道，伊布鲁替尼除了直接靶向白血病细胞外，还抑制这些细胞与T细胞、巨噬细胞和辅助细胞的相互作用。评估这些机制是很重要的，因为它们是非直接的抗白血病作用，并确定与长期用药有关的可能的副作用。本研究的目的是评估伊布鲁替尼对慢性淋巴细胞白血病T细胞亚群和细胞因子网络的体内影响。这项分析是在伊布鲁替尼治疗的第一个月期间对19名患者进行的。分别采用标准的多色流式细胞术和细胞微球阵列技术检测T细胞亚群和细胞因子/趋化因子。结果表明，伊布鲁替尼治疗可引起CLL患者T细胞亚群和细胞因子网络的改变。特别是，观察到外周血中T调节细胞的显著减少。通过靶向这些T细胞群，伊布鲁替尼可以刺激免疫系统对肿瘤细胞的排斥反应。
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.