当前位置: X-MOL 学术Blood Cancer J. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Activated naïve γδ T cells accelerate deep molecular response to BCR-ABL inhibitors in patients with chronic myeloid leukemia
Blood Cancer Journal ( IF 12.9 ) Pub Date : 2021-11-16 , DOI: 10.1038/s41408-021-00572-7
Yu-Cheng Chang , Yi-Hao Chiang , Kate Hsu , Chih-Kuang Chuang , Chen-Wei Kao , Yi-Fang Chang , Ming-Chih Chang , Ken-Hong Lim , Hung-I Cheng , Yen-Ning Hsu , Caleb G. Chen

Tyrosine kinase inhibitors (TKIs) that target BCR-ABL are the frontline treatments in chronic myeloid leukemia (CML). Growing evidence has shown that TKIs also enhance immunity. Since gamma-delta T (γδT) cells possess the potent anticancer capability, here we investigated the potential involvement of γδT cells in TKI treatments for CML. We characterized γδT cells isolated from chronic-phase CML patients before and during TKI treatments. γδT expression increased significantly in CML patients who achieved major molecular response (MMR) and deep molecular response (DMR). Their Vδ2 subset of γδT also expanded, and increased expression of activating molecules, namely IFN-γ, perforin, and CD107a, as well as γδT cytotoxicity. Mechanistically, TKIs augmented the efflux of isopentenyl pyrophosphate (IPP) from CML cells, which stimulated IFN-γ production and γδT expansion. Notably, the size of the IFN-γ+ naïve γδT population in TKI-treated CML patients was strongly correlated with their rates to reach DMR and with the duration on DMR. Statistical analysis suggests that a cutoff of 7.5% IFN-γ+ naïve subpopulation of γδT in CML patients could serve as a determinant for MR4.0 sustainability. Our results highlight γδT cells as a positive regulator for TKI responses in CML patients.



中文翻译:

活化的幼稚 γδ T 细胞加速慢性粒细胞白血病患者对 BCR-ABL 抑制剂的深度分子反应

靶向 BCR-ABL 的酪氨酸激酶抑制剂 (TKI) 是慢性粒细胞白血病 (CML) 的一线治疗药物。越来越多的证据表明,TKI 还可以增强免疫力。由于 γ-δ T (γδT) 细胞具有强大的抗癌能力,我们在此研究了 γδT 细胞在 TKI 治疗 CML 中的潜在作用。我们在 TKI 治疗之前和期间对从慢性期 CML 患者中分离出的 γδT 细胞进行了表征。γδT表达在达到主要分子学反应(MMR)和深度分子学反应(DMR)的CML患者中显着增加。它们的 γδT 的 Vδ2 子集也得到扩展,并增加了激活分子(即 IFN-γ、穿孔素和 CD107a)的表达,以及 γδT 细胞毒性。从机制上讲,TKIs 增加了 CML 细胞中异戊烯基焦磷酸 (IPP) 的流出,这刺激了 IFN-γ 的产生和 γδT 的扩增。值得注意的是,IFN-γ 的大小+ TKI 治疗的 CML 患者中的初始 γδT 人群与其达到 DMR 的比率和 DMR 持续时间密切相关。统计分析表明,CML 患者中 7.5% IFN-γ + γδT 幼稚亚群的截止值可以作为 MR 4.0可持续性的决定因素。我们的结果强调 γδT 细胞是 CML 患者 TKI 反应的正调节剂。

更新日期:2021-11-16
down
wechat
bug