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Immunology

The chronicles of T-cell exhaustion

Nature volume 543, pages 190–191 (2017)Cite this article

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T cells of the immune system often fail to target cancer cells because they enter a dysfunctional state known as exhaustion. Molecular analysis of T-cell exhaustion provides insights into the clinical use of these cells.

The T cells of the immune system that express the surface protein CD8 (CD8+ T cells) combat viral infection and cancer through their ability to 'search and destroy' infected or abnormal cells. However, CD8+ T cells often become dysfunctional, entering a state known as exhaustion, during certain chronic infections or when they enter a suppressive tumour microenvironment1. Although advances in immunotherapy have revealed that the immune system can be harnessed to fight cancer and other chronic diseases, much remains to be learnt about how T cells become dysfunctional and how they might be revitalized. Writing in Science, Pauken et al.2 and Sen et al.3 describe key molecular changes that occur in exhausted T cells. Their findings will improve our understanding of how these cells develop and whether their state can be manipulated by certain immunotherapies.

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Figure 1: Temporary reversal of T-cell exhaustion.

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Authors and Affiliations

  1. Robert A. Amezquita and Susan M. Kaech are in the Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.,

    Robert A. Amezquita & Susan M. Kaech

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  1. Robert A. Amezquita
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  2. Susan M. Kaech
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Correspondence to Robert A. Amezquita or Susan M. Kaech.

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Immunology: T-cell tweaks to target tumours

Immunology: Cytotoxic T cells that escape exhaustion

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Amezquita, R., Kaech, S. The chronicles of T-cell exhaustion. Nature 543, 190–191 (2017). https://doi.org/10.1038/nature21508

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