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[慢性髓性白血病与自然杀伤细胞免疫]

[Chronic myeloid leukemia and NK cell immunity].

作者信息

Ureshino Hiroshi, Shindo Takero, Tanaka Hidenori, Kimura Shinaya

机构信息

Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University.

Department of Hematology and Oncology, Kyoto University.

出版信息

Rinsho Ketsueki. 2017;58(4):381-388. doi: 10.11406/rinketsu.58.381.

Abstract

BCR-ABL1 tyrosine kinase inhibitors (TKIs) have dramatically improved the long-term outcomes of patients with chronic myelogenous leukemia (CML). Notably, approximately half of patients with a sustained deep molecular response experienced treatment free remission (TFR) even after discontinuation of TKI. Although antitumor immunity by natural killer (NK) cells might contribute to the effects of TKI and TFR in CML, the details of their actions have not as yet been elucidated. Recently, several reports have raised the possibility that the killer immunoglobulin-like receptor (KIR), a highly polymorphic NK cell receptor, may play important roles, because polymorphic patterns of KIR were shown to be associated with the intensity of clinical responses and outcomes in TKI-treated CML patients. Herein, we summarize genetic and immunological aspects of KIR, and also discuss the association between KIR and CML. If KIR polymorphism is actually associated with the outcomes of TKI-treated CML patients, we might be able to obtain prognostic information for patients and assess the possibility of TFR, which would not only benefit patients, but also provide a platform for improving the outcomes of other hematologic malignancies utilizing NK cell immunity.

摘要

BCR-ABL1酪氨酸激酶抑制剂(TKIs)显著改善了慢性髓性白血病(CML)患者的长期预后。值得注意的是,即使在停用TKI后,约一半获得持续深度分子反应的患者仍经历了无治疗缓解(TFR)。虽然自然杀伤(NK)细胞的抗肿瘤免疫可能有助于TKI和TFR在CML中的作用,但其作用细节尚未阐明。最近,一些报告提出了杀伤免疫球蛋白样受体(KIR)(一种高度多态的NK细胞受体)可能发挥重要作用的可能性,因为KIR的多态模式显示与TKI治疗的CML患者的临床反应强度和预后相关。在此,我们总结了KIR的遗传和免疫学方面,并讨论了KIR与CML之间的关联。如果KIR多态性确实与TKI治疗的CML患者的预后相关,我们或许能够获得患者的预后信息并评估TFR的可能性,这不仅将使患者受益,还将为利用NK细胞免疫改善其他血液系统恶性肿瘤的预后提供一个平台。

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