文章：

活化的初始γδ T细胞可加速慢性髓性白血病患者对BCR-ABL抑制剂产生深度分子学应答

Activated naïve γδ T cells accelerate deep molecular response to BCR-ABL inhibitors in patients with chronic myeloid leukemia

原文发布日期：2021-11-16

DOI: 10.1038/s41408-021-00572-7

类型: Article

开放获取: 是

英文摘要：

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.
 

摘要翻译： 

靶向BCR-ABL的酪氨酸激酶抑制剂（TKIs）是慢性粒细胞白血病（CML）的一线治疗方法。越来越多的证据表明TKIs还能增强免疫功能。鉴于γδT细胞具有强大的抗癌能力，本研究探讨了γδT细胞在CML患者TKI治疗中可能发挥的作用。我们对慢性期CML患者在TKI治疗前及治疗期间分离的γδT细胞进行了表征分析。结果显示，在达到主要分子反应（MMR）和深度分子反应（DMR）的CML患者中，γδT细胞表达显著增加。其γδT细胞的Vδ2亚群亦发生扩增，且激活分子（如IFN-γ、穿孔素和CD107a）的表达增强，γδT细胞的细胞毒性也随之提高。机制上，TKIs促进了CML细胞中异戊烯焦磷酸（IPP）的外排，从而刺激IFN-γ的产生和γδT细胞的扩增。值得注意的是，在TKI治疗的CML患者中，IFN-γ+初始γδT细胞亚群的规模与患者达到DMR的速率以及维持DMR的持续时间密切相关。统计分析表明，CML患者中IFN-γ+初始γδT亚群占比达到7.5%的临界值可作为维持MR4.0疗效的判定指标。我们的研究结果突显了γδT细胞在CML患者中对TKI治疗反应具有正向调控作用。

原文链接：

Activated naïve γδ T cells accelerate deep molecular response to BCR-ABL inhibitors in patients with chronic myeloid leukemia