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TRBV and TRBJ usage, when paired with specific HLA alleles, associates with distinct head and neck cancer survival rates.
Human Immunology ( IF 3.1 ) Pub Date : 2020-09-16 , DOI: 10.1016/j.humimm.2020.08.007
Mary F Arndt 1 , Darush M Koohestani 1 , Boris I Chobrutskiy 1 , Moody M Mihyu 1 , Michael Diaz 1 , Etienne C Gozlan 1 , Michelle Yeagley 1 , Saif Zaman 1 , Andrea M Roca 1 , George Blanck 2
Affiliation  

Common or dominant, T-cell receptor (TCR), V and J usage, in combination with particular human leukocyte antigen (HLA) alleles, has been associated with differing outcomes in viral infections, autoimmunity, and more recently, in cancer. Cervical cancer in particular represents the most dramatic series of distinctions of outcomes associated with differing combinations of dominant V or J usage and HLA alleles, possibly because of the strong association of cervical cancer with human papilloma virus (HPV), in turn leading to a likely molecular consistency in the mechanism of HPV antigen presentation. Thus, we considered assessing TRB V and J usage, HLA allele combinations, for their associations with survival rates and related data, in the cancer genome atlas head and neck cancer dataset. We obtained the TRB VDJ recombination reads from both the blood and tumor exome files and determined the V and J identities. We then established case ID (patient) subsets of V or J usage, HLA alleles, and determined, for example, that the TRBJ2-7, HLA-B*40:01 combination was associated with a better disease free survival rate than were either the TRBJ1-3, HLA-DPB1*03:01 or the TRBJ2-1, HLA-DPB1*02:01 combinations. Furthermore, these analyses led to the conclusion that TRBJ1-5 usage, and the HLA-C*08:02 and HLA-DRB1*03:01 alleles, had independent associations with distinct overall survival rates. In sum, the results suggest that dominant V or J usage, HLA allele combinations, and in certain cases, dominant V or J usage independently of HLA, could be useful in prognosis and in guiding immunotherapies.



中文翻译:

当与特定的 HLA 等位基因配对时,TRBV 和 TRBJ 的使用与不同的头颈癌存活率相关。

常见或显性 T 细胞受体 ( TCR )、VJ 的使用与特定的人类白细胞抗原 ( HLA ) 等位基因相结合,与病毒感染、自身免疫以及最近在癌症中的不同结果有关。宫颈癌尤其代表了与显性VJ用法和HLA等位基因的不同组合相关的最显着的一系列结果差异,这可能是因为宫颈癌与人乳头瘤病毒 (HPV) 的密切关联,进而导致可能HPV 抗原呈递机制的分子一致性。因此,我们考虑评估TRB VJ用法,HLA等位基因组合,因为它们与癌症基因组图谱头颈癌数据集中的存活率和相关数据的关联。我们从血液和肿瘤外显子组文件中获得了 TRB VDJ 重组读数,并确定了VJ身份。然后,我们建立了VJ用法、HLA等位基因的病例 ID(患者)子集,并确定,例如,TRBJ2-7、HLA-B*40:01组合与比任一组合更好的无病生存率相关在TRBJ1-3,HLA-DPB1 * 03:01TRBJ2-1,HLA-DPB1 * 02:01组合。此外,这些分析得出的结论是,TRBJ1-5 的使用以及HLA-C*08:02HLA-DRB1*03:01等位基因与不同的总生存率具有独立关联。总之,结果表明显性VJ使用、HLA等位基因组合,以及在某些情况下,独立于HLA 的显性VJ使用可用于预后和指导免疫治疗。

更新日期:2020-11-19
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