RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:NK cell defects: implication in acute myeloid leukemia.
NK cell defects: implication in acute myeloid leukemia.
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急性髓系白血病(AML)是一种复杂疾病,进展迅速,结局不佳/不令人满意。过去几年,重点一直放在开发AML的新疗法上;然而,复发仍然是一个重大问题。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的一个显著特征是激活性KIR受体的同源HLA配体低表达/不表达,因此这些肿瘤细胞逃避NK介导的裂解。近年来,不同的NK 细胞疗法已被用于治疗AML,例如过继性NK细胞输注、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,现有数据稀缺,且不同移植环境和不同类型白血病之间的结局存在差异。此外,其中一些疗法所获得的缓解仅持续很短时间。在这篇小型综述中,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,以及来自各种临床前和临床试验的结果。
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.
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