Mass cytometry has become an important technique for the deep analysis of single cell protein expression required for precision systems immunology. The ability to profile more than 40 markers per cell is particularly relevant for the differentiation of cell types for which low parametric characterization has proven difficult, such as exhausted CD8+ T cells (TEX). TEX with limited effector function accumulate in many chronic infections and cancers and are subject to inhibitory signaling mediated by several immune checkpoints (e.g., PD-1). Of note, TEX represent considerable targets for immune-stimulatory therapies and are beginning to be recognized as a major correlate of successful checkpoint blockade approaches targeting the PD-1 pathway. TEX exhibit substantial functional, transcriptomic and epigenomic differences compared to canonical functional T cell subsets [such as naïve (TN), effector (TEFF) and memory T cells (TMEM)]. However, phenotypic distinction of TEX from TEFF and TMEM can often be challenging since many molecules expressed by TEX can also be expressed by effector and memory T cell populations. Moreover, significant heterogeneity of TEX has been described, such as subpopulations of exhausted T cells with progenitor-progeny relationships or populations with different degrees of exhaustion or homeostatic potential that may directly inform about disease progression. In addition, TEX subsets have essential clinical implications as they differentially respond to antiviral and checkpoint therapies. The precise assessment of TEX thus requires a high-parametric analysis that accounts for differences to canonical T cell populations as well as for TEX subset heterogeneity. In this review, we discuss how mass cytometry can be used to reveal the role of TEX subsets in humans by combining exhaustion-directed phenotyping with functional profiling. Mass cytometry analysis of human TEX populations is instrumental to gain a better understanding of TEX in chronic infections and cancer. It has important implications for immune monitoring in therapeutic settings aiming to boost T cell immunity, such as during cancer immunotherapy.

中文翻译：

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使用质谱法分析人T细胞的消耗。

质谱分析法已成为深入分析精密系统免疫学所需的单细胞蛋白表达的一项重要技术。每个细胞分析40种以上标记的能力与已证明难以进行低参数表征的细胞类型的分化特别相关，例如疲惫的CD8 + T细胞（TEX）。具有有限的效应子功能的TEX在许多慢性感染和癌症中积累，并受到几种免疫检查点（例如PD-1）介导的抑制性信号传导。值得注意的是，TEX代表了免疫刺激疗法的重要靶点，并开始被公认为成功靶向PD-1途径的检查站封锁方法的主要相关因素。TEX表现出实质性的功能，与规范性功能性T细胞亚群[如幼稚（TN），效应子（TEFF）和记忆T细胞（TMEM）]相比，转录组和表观基因组差异。然而，TEX与TEFF和TMEM的表型区别通常是具有挑战性的，因为TEX表达的许多分子也可以由效应T细胞和记忆T细胞群体表达。此外，已描述了TEX的显着异质性，例如具有祖细胞-后代关系的精疲力竭的T细胞亚群，或具有不同程度的精疲力竭或体内平衡潜力的种群，这些种群可直接告知疾病进展。此外，TEX子集对抗病毒和检查点疗法的反应不同，因此具有重要的临床意义。因此，对TEX的精确评估需要进行高参数分析，该分析应考虑到典型T细胞群体的差异以及TEX子集的异质性。在这篇综述中，我们讨论了如何通过结合耗竭定向表型和功能性分析来利用细胞计数法揭示TEX子集在人类中的作用。人类TEX人群的大规模细胞计数分析有助于更好地了解TEX在慢性感染和癌症中的地位。它对旨在增强T细胞免疫力的治疗环境（例如癌症免疫治疗期间）的免疫监测具有重要意义。我们讨论了如何通过结合耗竭定向表型和功能性分析来利用细胞计数法揭示TEX子集在人类中的作用。人类TEX人群的大规模细胞计数分析有助于更好地了解TEX在慢性感染和癌症中的地位。它对旨在增强T细胞免疫力的治疗环境（例如癌症免疫治疗期间）的免疫监测具有重要意义。我们讨论了如何通过结合耗竭定向表型和功能性分析来利用细胞计数法揭示TEX子集在人类中的作用。人类TEX人群的大规模细胞计数分析有助于更好地了解TEX在慢性感染和癌症中的地位。它对旨在增强T细胞免疫力的治疗环境（例如癌症免疫治疗期间）的免疫监测具有重要意义。