CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
活化的初始γδ T 细胞加速慢性髓性白血病患者对 BCR-ABL 抑制剂的深度分子学反应
英文原题：Activated naïve γδ T cells accelerate deep molecular response to BCR-ABL inhibitors in patients with chronic myeloid leukemia.
查看英文原题
Activated naïve γδ T cells accelerate deep molecular response to BCR-ABL inhibitors in patients with chronic myeloid leukemia.
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中文摘要
靶向BCR-ABL的酪氨酸激酶抑制剂（TKIs）是慢性髓性白血病（CML）的一线治疗药物。越来越多的证据表明，TKIs还能增强免疫。由于γδT细胞具有强大的抗癌能力，本研究探讨了γδT细胞在CML的TKI治疗中的潜在参与。
我们对从慢性期CML患者TKI治疗前及治疗期间分离的γδT细胞进行了表征。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，γδT表达显著增加。其γδT的Vδ2亚群也扩增，活化分子即IFN-γ、穿孔素和CD107a的表达增加，以及γδT细胞毒性增强。在机制上，TKIs增强了异戊烯基焦磷酸（IPP）从CML细胞的外排，从而刺激IFN-γ产生和γδT扩增。
值得注意的是，在接受TKI治疗的CML患者中，IFN-γ+初始γδT细胞群体的大小与其达到DMR的比率以及DMR持续时间密切相关。统计分析提示，CML患者中γδT的IFN-γ+初始亚群7.5%的截断值可作为MR 4.0持续性的决定因素。
我们的结果突出表明，γδT细胞是CML患者TKI反应的积极调节因素。
展开英文摘要原文
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 MR 4. 0 sustainability.
Our results highlight γδT cells as a positive regulator for TKI responses in CML patients.
论文信息
- 作者
- Chang YC、Chiang YH、Hsu K、Chuang CK、Kao CW、Chang YF、Chang MC、Lim KH
- 第一作者单位
- Department of Hematology, MacKay Memorial Hospital, Taipei, 10449, Taiwan.Taiwan
- 通讯作者单位
- Department of Hematology, MacKay Memorial Hospital, Taipei, 10449, Taiwan. a0691@mail.mkc.edu.tw.Taiwan
- 文献类型
- 非美国政府资助研究
- 期刊
- Blood cancer journal2021 Nov 16
- 原文标识
- PubMed 34785653 · DOI 10.1038/s41408-021-00572-7
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