Successful treatment-free remission in chronic myeloid leukaemia and its association with reduced immune suppressors and increased natural killer cells
Successful treatment-free remission in chronic myeloid leukaemia and its association with reduced immune suppressors and increased natural killer cells
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DOI：
10.1111/bjh.16718
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发表时间：
2020-04-30
影响因子：
6.5
通讯作者：
Yong, Agnes S. M.
中科院分区：
文献类型：
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作者：
Irani, Yazad D.;Hughes, Amy;Yong, Agnes S. M.
目前没有生物标志物可以可靠地预测慢性粒细胞白血病（CML）的无治疗缓解（TFR）。我们在CML 8和CML 10临床研究的患者中描述了酪氨酸激酶抑制剂（TKI）停用时的效应和抑制免疫应答。在达到TFR的患者中，自然杀伤（NK）细胞活化NK受体表达增加。CD 4（+）或CD 8（+）T细胞比例无差异。此外，我们发现FoxP 3（+）调节性T细胞（T reg）和单核细胞髓源性抑制细胞（Mo-MDSC）在TFR患者中同时减少，表明免疫系统的效应臂和抑制臂协同工作以介导TFR。使用逻辑回归，使用发现队列（CML 10）生成预测模型。与低风险组相比，归类为高风险组的患者更有可能复发（HR 7中心点4，95% CI 2中心点9-19中心点1）。在独立的CML 8队列中成功验证了该模型（HR 8中心点3，95% CI 2中心点2-31中心点3）。TFR成功的有效预测可以通过效应-抑制因子评分获得，在TKI停止时使用绝对NK细胞、T reg和Mo-MDSC计数计算，反映免疫抑制因子和效应因子在成功TFR的免疫生物学中的贡献。
There is currently no biomarker that reliably predicts treatment-free remission (TFR) in chronic myeloid leukaemia (CML). We characterised effector and suppressor immune responses at the time of tyrosine kinase inhibitor (TKI) cessation in patients from the CML8 and CML10 clinical studies. Natural killer (NK) cells with increased expression of activating NK receptors were higher in patients who achieved TFR. There was no difference in the proportion of CD4(+) or CD8(+) T cells. Furthermore, we found that FoxP3(+) regulatory T cells (T reg) and monocytic myeloid-derived suppressor cells (Mo-MDSCs) were concomitantly decreased in TFR patients, suggesting that the effector and suppressor arms of the immune system work in concert to mediate TFR. A discovery cohort (CML10) was used to generate a predictive model, using logistic regression. Patients classified into the high-risk group were more likely to relapse when compared with the low-risk group (HR 7 center dot 4, 95% CI 2 center dot 9-19 center dot 1). The model was successfully validated on the independent CML8 cohort (HR 8 center dot 3, 95% CI 2 center dot 2-31 center dot 3). Effective prediction of TFR success may be obtained with an effector-suppressor score, calculated using absolute NK cell, T reg, and Mo-MDSC counts, at TKI cessation, reflecting the contribution of both immune suppressors and effectors in the immunobiology underlying successful TFR.