Metabolic and epigenetic regulation of T-cell exhaustion - PubMed (original) (raw)

Review

. 2020 Oct;2(10):1001-1012.

doi: 10.1038/s42255-020-00280-9. Epub 2020 Sep 21.

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Review

Metabolic and epigenetic regulation of T-cell exhaustion

Fabien Franco et al. Nat Metab. 2020 Oct.

Abstract

Current immunotherapies yield remarkable clinical outcomes by boosting the power of host immunity in cancer cell elimination and viral clearance. However, after prolonged antigen exposure, CD8+ T cells differentiate into a special differentiation state known as T-cell exhaustion, which poses one of the major hurdles to antiviral and antitumor immunity during chronic viral infection and tumour development. Growing evidence indicates that exhausted T cells undergo metabolic insufficiency with altered signalling cascades and epigenetic landscapes, which dampen effector immunity and cause poor responsiveness to immune-checkpoint-blockade therapies. How metabolic stress affects T-cell exhaustion remains unclear; therefore, in this Review, we summarize current knowledge of how T-cell exhaustion occurs, and discuss how metabolic insufficiency and prolonged stress responses may affect signalling cascades and epigenetic reprogramming, thus locking T cells into an exhausted state via specialized differentiation programming.

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References

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