文章：

HLA-A01和HLA-B27超型，而非HLA纯合性，与接受帕博利珠单抗联合化疗治疗的非小细胞肺癌患者临床结局相关

HLA-A01 and HLA-B27 Supertypes, but Not HLA Homozygocity, Correlate with Clinical Outcome among Patients with Non-Small Cell Lung Cancer Treated with Pembrolizumab in Combination with Chemotherapy

原文发布日期：7 September 2024

DOI: 10.3390/cancers16173102

类型: Article

开放获取: 是

英文摘要：

Introduction: Maximal heterozygosity on the human leukocyte antigen (HLA) loci has been found to be associated with improved survival and development of immune-related adverse events (irAEs) among NSCLC patients treated with immunotherapy. Here, we investigated the effect of germline HLA-I/-II on clinical outcomes among NSCLC patients treated with first-line pembrolizumab in combination with chemotherapy. Method: We prospectively recruited patients with NSCLC who were commencing first-line pembrolizumab in combination with chemotherapy. DNA from white blood cells was used for high-resolution HLA-I/II typing. Results: Of the 65 patients recruited, 53 complied with the inclusion criteria. We did not find an association between HLA-I/-II homozygosity and clinical outcome among the studied population. However, the presence of HLA-A01 was associated with unfavourable PFS (HR = 2.32, 95%CI 1.13–4.77,p= 0.022) and worsening OS (HR = 2.86, 95%CI 1.06–7.70,p= 0.038). The presence of HLA-B27 was associated with improved PFS (HR = 0.35, 95%CI 0.18–0.71,p= 0.004) and trends toward improving OS. None of the HLA-I supertypes were associated with the development or worsening of irAEs. Conclusions: The absence of association between genomic HLA-I/-II homozygosity and clinical outcome among patients with advanced NSCLC treated with pembrolizumab in combination with chemotherapy might reflect a diminished role for HLA molecules among patients with low or no PD-L1. HLA-A01 and HLA-B27 might have a role in predicting clinical outcomes among this cohort of patients. Further studies are needed to explore biomarkers for this group of patients.

摘要翻译： 

引言：既往研究发现，人类白细胞抗原（HLA）位点的最大杂合性与接受免疫治疗的NSCLC患者生存改善及免疫相关不良事件（irAEs）发生相关。本研究探讨了胚系HLA-I/-II对接受一线帕博利珠单抗联合化疗治疗的NSCLC患者临床结局的影响。方法：前瞻性纳入接受一线帕博利珠单抗联合化疗的NSCLC患者，采用白细胞DNA进行高分辨率HLA-I/II分型。结果：在入组的65例患者中，53例符合纳入标准。研究未发现HLA-I/-II纯合性与该人群临床结局存在关联。然而，HLA-A01的存在与较差的PFS（HR=2.32，95%CI 1.13-4.77，p=0.022）及恶化的OS（HR=2.86，95%CI 1.06-7.70，p=0.038）相关。HLA-B27的存在则与PFS改善（HR=0.35，95%CI 0.18-0.71，p=0.004）及OS改善趋势相关。所有HLA-I超型均与irAEs的发生或加重无关。结论：在接受帕博利珠单抗联合化疗的晚期NSCLC患者中，基因组HLA-I/-II纯合性与临床结局无关联性，这可能提示在PD-L1低表达或不表达患者中HLA分子的作用减弱。HLA-A01和HLA-B27可能对该患者群体的临床结局具有预测价值，需进一步研究探索该人群的生物标志物。

原文链接：

HLA-A01 and HLA-B27 Supertypes, but Not HLA Homozygocity, Correlate with Clinical Outcome among Patients with Non-Small Cell Lung Cancer Treated with Pembrolizumab in Combination with Chemotherapy