CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Application of T cell receptor (TCR) repertoire analysis for the advancement of cancer immunotherapy.
Application of T cell receptor (TCR) repertoire analysis for the advancement of cancer immunotherapy.
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T 细胞受体(TCR)测序已成为分析宿主-肿瘤相互作用的一种强大的新技术。下一代测序技术的进步,结合强大的新型生物信息学工具,使得能够对来自越来越多患有各种实体癌患者的肿瘤和血液样本中的免疫组库进行定量且可重复的表征。在这篇综述中,我们探讨如何从这些免疫组库中提取 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,我们探讨免疫组库之间 TCR 重叠的分析如何有助于界定抗肿瘤免疫应答的空间和时间异质性。最后,我们综述对单个 TCR 或来自相关 TCR 集合的 TCR 序列和结构的分析如何用于注释抗原特异性,这对个性化过继细胞免疫疗法的开发具有重要意义。
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.
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