文章：

肿瘤免疫治疗中T细胞的动力学和特异性

Dynamics and specificities of T cells in cancer immunotherapy

原文发布日期：2023-04-12

DOI: 10.1038/s41568-023-00560-y

类型: Review Article

开放获取: 否

英文摘要：

Recent advances in cancer immunotherapy — ranging from immune-checkpoint blockade therapy to adoptive cellular therapy and vaccines — have revolutionized cancer treatment paradigms, yet the variability in clinical responses to these agents has motivated intense interest in understanding how the T cell landscape evolves with respect to response to immune intervention. Over the past decade, the advent of multidimensional single-cell technologies has provided the unprecedented ability to dissect the constellation of cell states of lymphocytes within a tumour microenvironment. In particular, the rapidly expanding capacity to definitively link intratumoural phenotypes with the antigen specificity of T cells provided by T cell receptors (TCRs) has now made it possible to focus on investigating the properties of T cells with tumour-specific reactivity. Moreover, the assessment of TCR clonality has enabled a molecular approach to track the trajectories, clonal dynamics and phenotypic changes of antitumour T cells over the course of immunotherapeutic intervention. Here, we review the current knowledge on the cellular states and antigen specificities of antitumour T cells and examine how fine characterization of T cell dynamics in patients has provided meaningful insights into the mechanisms underlying effective cancer immunotherapy. We highlight those T cell subsets associated with productive T cell responses and discuss how diverse immunotherapies might leverage the pre-existing tumour-reactive T cell pool or instruct de novo generation of antitumour specificities. Future studies aimed at elucidating the factors associated with the elicitation of productive antitumour T cell immunity are anticipated to instruct the design of more efficacious treatment strategies.

摘要翻译： 

癌症免疫治疗的最新进展——从免疫检查点阻断疗法到过继性细胞疗法和疫苗——已经彻底改变了癌症治疗模式，但临床对这些药物反应的差异性引发了人们浓厚的兴趣，促使人们深入研究T细胞格局如何随着免疫干预反应而演变。过去十年中，多维单细胞技术的出现提供了前所未有的能力，能够解析肿瘤微环境中淋巴细胞状态的构成。特别是，快速发展的技术能够明确地将肿瘤内表型与T细胞受体（TCR）提供的T细胞抗原特异性联系起来，这使得聚焦研究具有肿瘤特异性反应性的T细胞特性成为可能。此外，对TCR克隆性的评估使得能够采用分子方法追踪免疫治疗干预过程中抗肿瘤T细胞的轨迹、克隆动态和表型变化。在此，我们回顾了当前关于抗肿瘤T细胞状态和抗原特异性的知识，并探讨了对患者T细胞动力学的精细表征如何为有效癌症免疫治疗的潜在机制提供了有意义的见解。我们重点强调了与高效T细胞反应相关的T细胞亚群，并讨论了不同的免疫疗法如何利用预先存在的肿瘤反应性T细胞库或指导从头产生抗肿瘤特异性。未来旨在阐明与引发高效抗肿瘤T细胞免疫相关因素的研究，预计将指导设计更有效的治疗策略。

原文链接：

Dynamics and specificities of T cells in cancer immunotherapy