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特定 TCR V-J 基因片段重排导致鉴定出与生存差异相关的泛 V-J CDR3:弥漫性大 B 细胞淋巴瘤。

Specific TCR V-J gene segment recombinations leading to the identification pan-V-J CDR3s associated with survival distinctions: diffuse large B-cell lymphoma.

机构信息

Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.

Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

出版信息

Leuk Lymphoma. 2022 Jun;63(6):1314-1322. doi: 10.1080/10428194.2021.2020781. Epub 2022 Jan 12.

Abstract

In the diffuse large B-cell lymphoma (DLBCL) setting, we examined lymph node biopsy, T-cell receptor features, and the DLBLC patient human leukocyte antigen (HLA) alleles, to provide a basis for assessing survival distinctions represented by the National Cancer Institute Center for Cancer Research (NCICCR) dataset. While previous analyses of other cancer datasets have indicated that specific T-cell receptor (TCR) V or J gene segments, independently, can be associated with a survival distinction, we have here identified V-J recombinations, representing specific V and J gene segments associated with survival distinctions. As specific V-J recombinations represent relatively conserved complementarity determining region-3 (CDR3) amino acid sequences, we assessed the entire DLBCL NCICCR dataset for such conserved CDR3 features. Overall, this approach indicated the opportunity of identifying DLBCL patient subpopulations with TCR CDR3 features, and HLA alleles, with significant survival distinctions, possibly identifying cohorts more likely to benefit from a given immunotherapy.

摘要

在弥漫性大 B 细胞淋巴瘤 (DLBCL) 环境中,我们检查了淋巴结活检、T 细胞受体特征以及 DLBLC 患者人类白细胞抗原 (HLA) 等位基因,为评估国家癌症研究所癌症研究中心 (NCICCR) 数据集所代表的生存差异提供了依据。虽然之前对其他癌症数据集的分析表明,特定的 T 细胞受体 (TCR) V 或 J 基因片段可以独立地与生存差异相关,但我们在这里确定了 V-J 重组,代表与生存差异相关的特定 V 和 J 基因片段。由于特定的 V-J 重组代表相对保守的互补决定区 3 (CDR3) 氨基酸序列,我们评估了整个 NCICCR DLBCL 数据集的这种保守的 CDR3 特征。总的来说,这种方法表明有可能确定具有 TCR CDR3 特征和 HLA 等位基因的 DLBCL 患者亚群,这些患者具有显著的生存差异,可能确定更有可能从特定免疫治疗中获益的队列。

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