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CD8+ T cell states in human cancer: insights from single-cell analysis.
Nature Reviews Cancer ( IF 72.5 ) Pub Date : 2020-02-05 , DOI: 10.1038/s41568-019-0235-4 Anne M van der Leun 1 , Daniela S Thommen 1 , Ton N Schumacher 1
Nature Reviews Cancer ( IF 72.5 ) Pub Date : 2020-02-05 , DOI: 10.1038/s41568-019-0235-4 Anne M van der Leun 1 , Daniela S Thommen 1 , Ton N Schumacher 1
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The T cell infiltrates that are formed in human cancers are a modifier of natural disease progression and also determine the probability of clinical response to cancer immunotherapies. Recent technological advances that allow the single-cell analysis of phenotypic and transcriptional states have revealed a vast heterogeneity of intratumoural T cell states, both within and between patients, and the observation of this heterogeneity makes it critical to understand the relationship between individual T cell states and therapy response. This Review covers our current knowledge of the T cell states that are present in human tumours and the role that different T cell populations have been hypothesized to play within the tumour microenvironment, with a particular focus on CD8+ T cells. The three key models that are discussed herein are as follows: (1) the dysfunction of T cells in human cancer is associated with a change in T cell functionality rather than inactivity; (2) antigen recognition in the tumour microenvironment is an important driver of T cell dysfunctionality and the presence of dysfunctional T cells can hence be used as a proxy for the presence of a tumour-reactive T cell compartment; (3) a less dysfunctional population of tumour-reactive T cells may be required to drive a durable response to T cell immune checkpoint blockade.
中文翻译：
人类癌症中的CD8 + T细胞状态：单细胞分析的见解。
在人类癌症中形成的T细胞浸润是自然疾病进展的调节剂，并且还决定了对癌症免疫疗法产生临床反应的可能性。允许对表型和转录状态进行单细胞分析的最新技术进展表明，患者体内和患者之间的肿瘤内T细胞状态具有巨大的异质性，对这种异质性的观察使其成为理解单个T细胞状态之间关系的关键。和治疗反应。这篇综述涵盖了我们目前对人类肿瘤中存在的T细胞状态的了解，以及已经假设不同的T细胞群体在肿瘤微环境中发挥的作用，特别是CD8 + T细胞。本文讨论的三个关键模型如下：（1）人类癌症中T细胞功能异常与T细胞功能性改变而非失活有关；（2）肿瘤微环境中的抗原识别是T细胞功能失调的重要驱动力，因此功能失调的T细胞的存在可以用作肿瘤反应性T细胞区室的代表。（3）可能需要较少功能失调的肿瘤反应性T细胞群来驱动对T细胞免疫检查点封锁的持久反应。
更新日期：2020-02-05
中文翻译：
人类癌症中的CD8 + T细胞状态：单细胞分析的见解。
在人类癌症中形成的T细胞浸润是自然疾病进展的调节剂，并且还决定了对癌症免疫疗法产生临床反应的可能性。允许对表型和转录状态进行单细胞分析的最新技术进展表明，患者体内和患者之间的肿瘤内T细胞状态具有巨大的异质性，对这种异质性的观察使其成为理解单个T细胞状态之间关系的关键。和治疗反应。这篇综述涵盖了我们目前对人类肿瘤中存在的T细胞状态的了解，以及已经假设不同的T细胞群体在肿瘤微环境中发挥的作用，特别是CD8 + T细胞。本文讨论的三个关键模型如下：（1）人类癌症中T细胞功能异常与T细胞功能性改变而非失活有关；（2）肿瘤微环境中的抗原识别是T细胞功能失调的重要驱动力，因此功能失调的T细胞的存在可以用作肿瘤反应性T细胞区室的代表。（3）可能需要较少功能失调的肿瘤反应性T细胞群来驱动对T细胞免疫检查点封锁的持久反应。
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