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与特定人类白细胞抗原(HLA)等位基因配对的T细胞受体V和J的使用情况与宫颈癌的不同生存率相关。

T-cell receptor V and J usage paired with specific HLA alleles associates with distinct cervical cancer survival rates.

作者信息

Roca Andrea M, Chobrutskiy Boris I, Callahan Blake M, Blanck George

机构信息

Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, United States.

Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, United States; Immunology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States.

出版信息

Hum Immunol. 2019 Apr;80(4):237-242. doi: 10.1016/j.humimm.2019.01.005. Epub 2019 Jan 23.

Abstract

Cervical cancer is more strongly associated with a specific virus, Human Papilloma Virus (HPV), in otherwise healthy individuals, than is any other cancer. Thus, there is an expectation that an adaptive immune signature of cervical cancer would be highly apparent. Here we used a genomics approach to investigate the relationship between T-cell receptor (TCR) V and J usage and survival for patients diagnosed with cervical cancer, relying exclusively on tissue and blood exome files. Specific TCR V or J segments, identified in recombination reads recovered from the exome files, were combined with the patient HLA alleles to identify V or J, HLA allele combination groups associated with distinct survival rates. For examples, the T-cell receptor-β (TRB) V6-5, HLA-A02:01 combination was associated with a positive outcome, and the TRBV6-1, HLA-A01:01 combination was associated with a negative outcome. Overall, these results point to V or J usage, HLA allele combinations as survival biomarkers, likely conveniently accessible with a noninvasive procedure, and the results may point the way towards immunological reagents useful in therapy designs.

摘要

在其他方面健康的个体中,宫颈癌与一种特定病毒——人乳头瘤病毒(HPV)的关联比其他任何癌症都更为紧密。因此,人们期望宫颈癌的适应性免疫特征会非常明显。在这里,我们采用基因组学方法,仅依靠组织和血液外显子文件,研究了诊断为宫颈癌的患者的T细胞受体(TCR)V和J基因片段使用情况与生存率之间的关系。从外显子文件中恢复的重组读数中识别出的特定TCR V或J基因片段,与患者的HLA等位基因相结合,以识别与不同生存率相关的V或J、HLA等位基因组合组。例如,T细胞受体-β(TRB)V6-5、HLA-A02:01组合与良好预后相关,而TRBV6-1、HLA-A01:01组合与不良预后相关。总体而言,这些结果表明V或J基因片段使用情况、HLA等位基因组合可作为生存生物标志物,可能通过无创程序方便地获取,并且这些结果可能为治疗设计中有用的免疫试剂指明方向。

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