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首页> 外文期刊>Annual Review of Immunology >CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer
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CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer

机译：慢性病毒感染和癌症期间CD8 T细胞耗尽

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摘要

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 alpha PD-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.
机译：耗尽的CD8 T（TEX）细胞是一种不同的细胞谱系，其在动物模型和人类中的慢性感染和癌症期间出现。 Tex细胞的特征在于累积效应功能，高且持续的抑制剂的表达，代谢性失调，记忆召回和稳态自我更新，以及不同的转录和表观遗传程序的逐次丧失。通过抑制受体阻断重新加入Tex细胞的能力，例如αPD-1，突出了靶向该群体的治疗潜力。新兴洞察疲惫机制正在通知免疫治疗癌症和慢性感染。然而，与其他免疫细胞一样，Tex细胞是异构的并且包括祖先和端子子集，具有独特的特性和对检查点封锁的响应。在这里，我们审查目前对TEX细胞生物学的理解，包括发育路径，转录和表观遗传特征，以及有助于耗尽的细胞内在和外在因素，以及该知识如何通知慢性感染，自身免疫和癌症中TEX细胞的治疗靶向。

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