文章：

KIR-HLA基因型对基于自然杀伤细胞的免疫疗法预防活体肝移植后肝细胞癌的影响

Impact of KIR-HLA Genotype on Natural-Killer-Cell-Based Immunotherapy for Preventing Hepatocellular Carcinoma after Living-Donor Liver Transplantation

原文发布日期：26 January 2024

DOI: 10.3390/cancers16030533

类型: Article

开放获取: 是

英文摘要：

Natural killer (NK) cells have immunosurveillance potential in hepatocellular carcinoma (HCC). We performed adaptive immunotherapy using donor-liver-derived natural killer (NK) cells after living-donor liver transplantation (LDLT) to prevent HCC recurrence. Dominant inhibitory signals tightly regulate NK cell activity via human leukocyte antigen (HLA)-specific inhibitory receptors, such as killer immunoglobulin-like receptors (KIRs). The functional recognition of HLA through KIR raises the NK cell capacity, which is a process termed “licensing.” Here, we investigated the effect of polymorphic KIR-HLA genotypes on the efficacy of NK-cell-based immunotherapy after LDLT. Seventy-seven Japanese recipients with HCC who underwent LDLT and their corresponding donors between 1996 and 2016 were enrolled in this study. The median follow-up period was 8.3 years. The HCC recurrence risk was stratified using radiological and pathological assessments according to the Milan criteria. Of the 77 recipients, 38 received immunotherapy. Immunotherapy improves early post-transplantation survival and lowers the recurrence rate in the intermediate-risk recipients. We analyzed the genotypes of five inhibitory KIRs and HLA using sequence-specific polymorphism-based typing. The polymorphic KIR-HLA genotype revealed that genetically vulnerable liver transplant recipients with a poorly licensed NK genotype have an improved prognosis by immunotherapy with donor-liver-derived NK cells. Thus, the combination of recipient and donor KIR-HLA genotypes is worthy of attention for further investigation, especially considering the clinical application of NK-cell-based immunotherapy.

摘要翻译： 

自然杀伤（NK）细胞在肝细胞癌（HCC）中具有免疫监视潜力。我们在活体肝移植（LDLT）后使用供肝来源的自然杀伤（NK）细胞进行适应性免疫治疗，以预防HCC复发。NK细胞活性主要通过人类白细胞抗原（HLA）特异性抑制受体（如杀伤细胞免疫球蛋白样受体，KIR）的显性抑制信号进行严格调控。通过KIR对HLA的功能性识别可提升NK细胞能力，这一过程称为“许可”。本研究探讨了多态性KIR-HLA基因型对LDLT后基于NK细胞的免疫治疗效果的影响。本研究纳入了1996年至2016年间接受LDLT的77例日本HCC受者及其对应供者。中位随访期为8.3年。根据米兰标准，通过影像学和病理学评估对HCC复发风险进行分层。在77例受者中，38例接受了免疫治疗。免疫治疗改善了中危受者的移植后早期生存率并降低了复发率。我们采用基于序列特异性多态性的分型方法分析了五种抑制性KIR及HLA的基因型。多态性KIR-HLA基因型分析显示，对于具有低许可NK基因型的遗传易感性肝移植受者，采用供肝来源NK细胞的免疫治疗可改善其预后。因此，结合受者与供者的KIR-HLA基因型值得进一步研究关注，特别是在考虑基于NK细胞的免疫治疗的临床应用时。

原文链接：

Impact of KIR-HLA Genotype on Natural-Killer-Cell-Based Immunotherapy for Preventing Hepatocellular Carcinoma after Living-Donor Liver Transplantation