Division of Immunology, The Netherlands Cancer Institute (NKI-AVL), Amsterdam, the Netherlands.
Immunol Rev. 2014 Jan;257(1):72-82. doi: 10.1111/imr.12140.
The infiltration of human tumors by T cells is a common phenomenon, and over the past decades, it has become increasingly clear that the nature of such intratumoral T-cell populations can predict disease course. Furthermore, intratumoral T cells have been utilized therapeutically in clinical studies of adoptive T-cell therapy. In this review, we describe how novel methods that are either based on T-cell receptor (TCR) sequencing or on cancer exome analysis allow the analysis of the tumor reactivity and antigen-specificity of the intratumoral TCR repertoire with unprecedented detail. Furthermore, we discuss studies that have started to utilize these techniques to probe the link between cancer exomes and the intratumoral TCR pool. Based on the observation that both the cancer epitope repertoire and intratumoral TCR repertoire appear highly individual, we outline strategies, such as 'autologous TCR gene therapy', that exploit the tumor-resident TCR repertoire for the development of personalized immunotherapy.
肿瘤组织中 T 细胞的浸润是一种常见现象，在过去几十年中，越来越明显的是，这种肿瘤内 T 细胞群体的性质可以预测疾病的进程。此外，肿瘤内 T 细胞已在过继性 T 细胞治疗的临床研究中得到了治疗应用。在这篇综述中，我们描述了基于 T 细胞受体 (TCR) 测序或癌症外显子组分析的新方法如何以前所未有的细节分析肿瘤内 TCR 库的肿瘤反应性和抗原特异性。此外，我们还讨论了一些已经开始利用这些技术来探讨癌症外显子组与肿瘤内 TCR 库之间联系的研究。基于观察到癌症表位库和肿瘤内 TCR 库都表现出高度的个体性，我们概述了一些策略，如“自体 TCR 基因治疗”，利用肿瘤驻留的 TCR 库来开发个性化免疫疗法。
