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基于血液的 T 细胞受体抗病毒 CDR3 与神经母细胞瘤患者总生存率降低相关。

Blood-based T cell receptor anti-viral CDR3s are associated with worse overall survival for neuroblastoma.

机构信息

College of Medicine, University of Central Florida, Orlando, FL, 32827, USA.

Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Bd. MDC7, Tampa, FL, 33612, USA.

出版信息

J Cancer Res Clin Oncol. 2023 Oct;149(13):12047-12056. doi: 10.1007/s00432-023-05059-5. Epub 2023 Jul 8.

Abstract

With the advent of large collections of adaptive immune receptor recombination reads representing cancer, there is the opportunity to further investigate the adaptive immune response to viruses in the cancer setting. This is a particularly important goal due to longstanding but still not well-resolved questions about viral etiologies in cancer and viral infections as comorbidities. In this report, we assessed the T cell receptor complementarity determining region-3 (CDR3) amino acid (AA) sequences, for blood-sourced TCRs from neuroblastoma (NBL) cases, for exact AA sequence matches to previously identified anti-viral TCR CDR3 AA sequences. Results indicated the presence of anti-viral TCR CDR3 AA sequences in the NBL blood samples highly significantly correlated with worse overall survival. Furthermore, the TCR CDR3 AA sequences demonstrating chemical complementarity to many cytomegalovirus antigens represented cases with a worse outcome, including cases where such CDR3s were obtained from tumor samples. Overall, these results indicate a significant need for, and provide a novel strategy for assessing viral infection complications in NBL patients.

摘要

随着大量代表癌症的适应性免疫受体重组阅读的出现,有机会进一步研究癌症环境中的适应性免疫对病毒的反应。由于癌症病毒病因和病毒感染作为合并症的长期存在但仍未得到很好解决的问题,这是一个特别重要的目标。在本报告中,我们评估了神经母细胞瘤(NBL)病例血液源 T 细胞受体(TCR)的 T 细胞受体互补决定区-3(CDR3)氨基酸(AA)序列,以确定与先前鉴定的抗病毒 TCR CDR3 AA 序列的完全 AA 序列匹配。结果表明,NBL 血液样本中存在抗病毒 TCR CDR3 AA 序列与总体生存较差高度相关。此外,与许多巨细胞病毒抗原表现出化学互补性的 TCR CDR3 AA 序列代表预后较差的病例,包括从肿瘤样本中获得此类 CDR3 的病例。总体而言,这些结果表明迫切需要并提供了一种新策略来评估 NBL 患者的病毒感染并发症。

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