CD8(+) T Cell Exhaustion in Cancer.

CD8(+) T Cell Exhaustion in Cancer.
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DOI:
10.3389/fimmu.2021.715234
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发表时间:
2021
影响因子:
7.3
通讯作者:
Salek-Ardakani S
Salek-Ardakani S
中科院分区:
医学2区
文献类型:
--
作者:
Dolina JS;Van Braeckel-Budimir N;Thomas GD;Salek-Ardakani S

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对耗尽的CD8+T细胞(TeX)谱系的理解正在发生范式转变。单细胞分析最初被认为是一个统一的群体,对持久性抗原的反应会逐渐丧失效应器功能,现在单细胞分析发现CD8+TeX由多个相互关联的亚群组成。CD8+TeX细胞系内的异质性包括免疫检查点阻断(ICB)允许性和难治性亚群,分别称为干细胞样细胞和终末分化细胞。这些群体占据着不同的外周和肿瘤内的利基环境,并以控制细胞状态之间转换的转录过程为特征。这篇综述介绍了该领域的主要发现,以构建一个关于抗肿瘤CD8+TeX的空间、转录和功能异质性的最新观点。这些新的见解广泛地呼吁(重新)将癌症免疫治疗的重点放在CD8+TeX发育连续体的驱动机制上(S),旨在稳定功能亚群。
A paradigm shift in the understanding of the exhausted CD8+ T cell (Tex) lineage is underway. Originally thought to be a uniform population that progressively loses effector function in response to persistent antigen, single-cell analysis has now revealed that CD8+ Tex is composed of multiple interconnected subpopulations. The heterogeneity within the CD8+ Tex lineage is comprised of immune checkpoint blockade (ICB) permissive and refractory subsets termed stem-like and terminally differentiated cells, respectively. These populations occupy distinct peripheral and intratumoral niches and are characterized by transcriptional processes that govern transitions between cell states. This review presents key findings in the field to construct an updated view of the spatial, transcriptional, and functional heterogeneity of anti-tumoral CD8+ Tex. These emerging insights broadly call for (re-)focusing cancer immunotherapies to center on the driver mechanism(s) underlying the CD8+ Tex developmental continuum aimed at stabilizing functional subsets.
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