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作者：SCI天天读
SCI
14 May 2023
Dynamics and specificities of T cells in cancer immunotherapy
（Nature reviews. Cancer，IF：69.8）
Oliveira G, Wu CJ. Dynamics and specificities of T cells in cancer immunotherapy. Nat Rev Cancer. 2023 May;23(5):295-316. doi: 10.1038/s41568-023-00560-y. Epub 2023 Apr 12. PMID: 37046001.
Authors ：Giacomo Oliveira，Catherine J. Wu
Correspondence ：giacomo_oliveira@dfci.harvard.edu，cwu@partners.org
Abstract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.
癌症免疫疗法的新进展—从免疫检查点阻断疗法到输入细胞疗法和疫苗—彻底改变了癌症治疗模式，然而，对这些药物的临床反应的差异激发了人们对免疫干预的反应相关的T细胞图谱如何演变的浓厚兴趣。近十年来，多维单细胞技术的出现为剖析肿瘤微环境中淋巴细胞的细胞状态群提供了前所未有的能力。特别是，其迅速增强的能力明确地将肿瘤内表型和由T细胞受体（TCRs）所提供的T细胞的抗原特异性联系起来，现在使我们能够专注于研究具有肿瘤特异性反应性的T细胞的特性。此外，TCR克隆性的评估使分子方法能够跟踪免疫治疗干预过程中抗肿瘤T细胞轨迹、克隆的动态变化和表型变化。在此，我们回顾了目前关于抗肿瘤T细胞的细胞状态和抗原特异性的认知，并研究了患者T细胞动态变化的精细表征是如何为有效癌症免疫治疗的机制提供有意义的见解。我们重点介绍了与生产性T细胞反应相关的T细胞亚群，并讨论了多种免疫疗法如何利用先前存在的肿瘤反应性T细胞池或指导抗肿瘤特异性的从头生成。未来旨在阐明诱导产生性抗肿瘤T细胞免疫相关因素的研究有望指导设计更有效的治疗策略。
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原文地址：http://mp.weixin.qq.com/s?src=11×tamp=1684073715&ver=4528&signature=yvfglahTXx0QWc46bLfDLnG3x-YQQdPV7HTgRQqoE52y8kNqhdklk4UBpV5yy77MSKFUPqu8OtizEG9X*dqS7afAhjxEIj7kvUNfqvt6yByrdETluecKw4gwcQj-y*D3&new=1 |
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