Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, metabolic dysregulation, poor memory recall and homeostatic self-renewal, and distinct transcriptional and epigenetic programs. The ability to reinvigorate Tex cells through inhibitory receptor blockade, such as αPD-1, highlights the therapeutic potential of targeting this population. Emerging insights into the mechanisms of exhaustion are informing immunotherapies for cancer and chronic infections. However, like other immune cells, Tex cells are heterogeneous and include progenitor and terminal subsets with unique characteristics and responses to checkpoint blockade. Here, we review our current understanding of Tex cell biology, including the developmental paths, transcriptional and epigenetic features, and cell intrinsic and extrinsic factors contributing to exhaustion and how this knowledge may inform therapeutic targeting of Tex cells in chronic infections, autoimmunity, and cancer.

中文翻译：

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慢性病毒感染和癌症期间的CD8 T细胞衰竭。

耗尽的CD8 T（Tex）细胞是在动物模型和人类的慢性感染和癌症期间出现的独特细胞谱系。Tex细胞的特征是效应器功能逐渐丧失，抑制受体高而持续表达，代谢失调，记忆力差和体内自我更新能力差，以及独特的转录和表观遗传程序。通过抑制性受体阻断（例如αPD-1）使Tex细胞恢复活力的能力凸显了针对该人群的治疗潜力。精疲力尽的机制的新见识为癌症和慢性感染的免疫疗法提供了信息。但是，与其他免疫细胞一样，Tex细胞也是异质的，包括具有独特特征和对关卡封锁反应的祖细胞和末端亚群。这里，