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Annual Review of Immunology

Volume 37, 2019

CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer

Abstract

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.

Keyword(s): cancer, chronic viral infections, immunotherapy, inhibitory receptors, PD-1, T cell exhaustion
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/content/journals/10.1146/annurev-immunol-041015-055318
2019-04-26
2024-04-19
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CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer
Annual Review of Immunology 37, 457 (2019); https://doi.org/10.1146/annurev-immunol-041015-055318
/content/journals/10.1146/annurev-immunol-041015-055318
/content/journals/10.1146/annurev-immunol-041015-055318
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