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Application of T cell receptor (TCR) repertoire analysis for the advancement of cancer immunotherapy
Current Opinion in Immunology ( IF 6.6 ) Pub Date : 2021-08-25 , DOI: 10.1016/j.coi.2021.07.006
Kroopa Joshi 1 , Martina Milighetti 2 , Benjamin M Chain 3
Affiliation  

T cell receptor (TCR) sequencing has emerged as a powerful new technology in analysis of the host–tumour interaction. The advances in NextGen sequencing technologies, coupled with powerful novel bioinformatic tools, allow quantitative and reproducible characterisation of repertoires from tumour and blood samples from an increasing number of patients with a variety of solid cancers. In this review, we consider how global metrics such as T cell clonality and diversity can be extracted from these repertoires and used to give insight into the mechanism of action of immune checkpoint blockade. Furthermore, we explore how the analysis of TCR overlap between repertories can help define spatial and temporal heterogeneity of the anti-tumoural immune response. Finally, we review how analysis of TCR sequence and structure, either of individual TCRs or from sets of related TCRs can be used to annotate the antigenic specificity, with important implications for the development of personalised adoptive cellular immunotherapies.



中文翻译:


T细胞受体(TCR)谱分析在癌症免疫治疗进展中的应用



T 细胞受体 (TCR) 测序已成为分析宿主与肿瘤相互作用的强大新技术。 NextGen 测序技术的进步,加上强大的新型生物信息学工具,可以对来自越来越多的各种实体癌患者的肿瘤和血液样本的库进行定量和可重复的表征。在这篇综述中,我们考虑如何从这些库中提取 T 细胞克隆性和多样性等全局指标,并用于深入了解免疫检查点阻断的作用机制。此外,我们探讨了对库之间 TCR 重叠的分析如何帮助定义抗肿瘤免疫反应的空间和时间异质性。最后,我们回顾了如何使用单个 TCR 或相关 TCR 组的 TCR 序列和结构分析来注释抗原特异性,这对个性化过继细胞免疫疗法的开发具有重要意义。

更新日期:2021-08-26
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