Natural Killer Cells Offer Differential Protection From Leukemia in Chinese Southern Han
Natural Killer Cells Offer Differential Protection From Leukemia in Chinese Southern Han
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DOI：
10.3389/fimmu.2019.01646
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发表时间：
2019-07-16
影响因子：
7.3
通讯作者：
Norman, Paul J.
中科院分区：
文献类型：
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作者：
Deng, Zhihui;Zhao, Jun;Norman, Paul J.
人类自然杀伤 (NK) 细胞抑制性受体与多态性 HLA-A、-B 和 -C 分子的相互作用可训练 NK 细胞对肿瘤细胞进行免疫监视。 KIR A 单倍型编码一组独特的 HLA 特异性 NK 细胞抑制受体，对免疫具有强烈影响。我们观察到，745 名健康的中国南方汉族人中 KIR A 纯合性频率高于代表三种类型白血病的 836 名成年患者：ALL（OR = 0.68，95% CI = 0.52-0.89，p = 0.004）、AML（OR = 0.76，95% CI = 0.59-0.98，p = 0.034）和 CML （OR = 0.72 95% CI = 0.51-1.0，ns）。我们在 NHL 中观察到相同的趋势（OR = 0.47 95% CI = 0.26-0.88 p = 0.017）。对于 ALL，在 KIR 配体 C1 (Pc = 0.01) 和 Bw4 (Pc = 0.001) 存在的情况下，KIR AA 基因型的保护作用更大，这两种配体在东亚人中紧密相连。相比之下，C2 配体增强了对 CML 的保护（Pc = 0.004）。从 KIR AA 个体中分离的 NK 细胞对白血病细胞的细胞毒性显着高于其他 KIR 基因型的细胞 (p < 0.0001)。这些数据表明东亚 KIR A 单倍型编码的 KIR 同种异型具有强烈的抑制性，使 NK 细胞能够对 HLA 表达改变的白血病细胞做出反应。因此，对具有不同 KIR 和 HLA 分布的人群的研究有助于理解显着影响白血病发病机制的免疫机制。
Interactions of human natural killer (NK) cell inhibitory receptors with polymorphic HLA-A, -B and -C molecules educate NK cells for immune surveillance against tumor cells. The KIR A haplotype encodes a distinctive set of HLA-specific NK cell inhibiting receptors having strong influence on immunity. We observed higher frequency of KIR A homozygosity among 745 healthy Chinese Southern Han than 836 adult patients representing three types of leukemia: ALL (OR = 0.68, 95% CI = 0.52-0.89, p = 0.004), AML (OR = 0.76, 95% CI = 0.59-0.98, p = 0.034), and CML (OR = 0.72 95% CI = 0.51-1.0, ns). We observed the same trend for NHL (OR = 0.47 95% CI = 0.26-0.88 p = 0.017). For ALL, the protective effect of the KIR AA genotype was greater in the presence of KIR ligands C1 (Pc = 0.01) and Bw4 (Pc = 0.001), which are tightly linked in East Asians. By contrast, the C2 ligand strengthened protection from CML (Pc = 0.004). NK cells isolated from KIR AA individuals were significantly more cytotoxic toward leukemic cells than those from other KIR genotypes (p < 0.0001). These data suggest KIR allotypes encoded by East Asian KIR A haplotypes are strongly inhibitory, arming NK cells to respond to leukemogenic cells having altered HLA expression. Thus, the study of populations with distinct KIR and HLA distributions enlightens understanding of immune mechanisms that significantly impact leukemia pathogenesis.