Transplant Immunology and Immunogenetics Lab, Advanced Centre for Treatment, Education and Research in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, India.
Homi Bhabha National Institute, Mumbai, India.
Front Immunol. 2023 May 9;14:1112059. doi: 10.3389/fimmu.2023.1112059. eCollection 2023.
Acute Myeloid Leukemia (AML) is a complex disease with rapid progression and poor/unsatisfactory outcomes. In the past few years, the focus has been on developing newer therapies for AML; however, relapse remains a significant problem. Natural Killer cells have strong anti-tumor potential against AML. This NK-mediated cytotoxicity is often restricted by cellular defects caused by disease-associated mechanisms, which can lead to disease progression. A stark feature of AML is the low/no expression of the cognate HLA ligands for the activating KIR receptors, due to which these tumor cells evade NK-mediated lysis. Recently, different Natural Killer cell therapies have been implicated in treating AML, such as the adoptive NK cell transfer, Chimeric antigen receptor-modified NK (CAR-NK) cell therapy, antibodies, cytokine, and drug treatment. However, the data available is scarce, and the outcomes vary between different transplant settings and different types of leukemia. Moreover, remission achieved by some of these therapies is only for a short time. In this mini-review, we will discuss the role of NK cell defects in AML progression, particularly the expression of different cell surface markers, the available NK cell therapies, and the results from various preclinical and clinical trials.
急性髓系白血病（AML）是一种复杂的疾病，具有快速进展和较差/不满意的结果。在过去的几年中，人们一直致力于开发治疗 AML 的新疗法；然而，复发仍然是一个重大问题。自然杀伤 (NK) 细胞对 AML 具有强大的抗肿瘤潜力。这种 NK 介导的细胞毒性通常受到疾病相关机制引起的细胞缺陷的限制，这可能导致疾病进展。AML 的一个显著特征是其对激活性杀伤细胞免疫球蛋白样受体（KIR）配体的低/无表达，由于这些肿瘤细胞逃避了 NK 介导的裂解。最近，不同的 NK 细胞疗法已被用于治疗 AML，例如过继性 NK 细胞转移、嵌合抗原受体修饰的 NK（CAR-NK）细胞疗法、抗体、细胞因子和药物治疗。然而，可用的数据很少，并且不同移植环境和不同类型的白血病之间的结果存在差异。此外，这些疗法中的一些所实现的缓解只是暂时的。在这篇迷你综述中，我们将讨论 NK 细胞缺陷在 AML 进展中的作用，特别是不同细胞表面标志物的表达、可用的 NK 细胞疗法以及各种临床前和临床试验的结果。
