Metabolic exhaustion in infection, cancer and autoimmunity


It has become increasingly clear that changes in metabolism are not just consequences of T cell activation but instead are also essential drivers of that process that shape the extent and nature of differentiation and function. The process of T cell exhaustion has been linked to the outcome of chronic immune responses in multiple contexts, including chronic infection, cancer and autoimmunity. Factors that regulate the development and maintenance of exhaustion are of increasing interest as targets of therapeutic modulation. Studies have shown T cell immunometabolism to be integral to the control and development of T cell exhaustion. Early metabolic changes are responsible for the later emergence of exhaustion, do not simply reflect changes secondary to chronic activation and are modifiable. Increased understanding of this metabolic control promises to improve the ability to modulate T cell immunity to chronic antigen stimulation in multiple contexts.

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Fig. 1: Balance between effector T cells and memory T cells and the associated metabolic pathways.

Marina Corral Spence/Springer Nature.

Fig. 2: Hypoxia and effector differentiation of T cells.

Marina Corral Spence/Springer Nature.

Fig. 3: Exhaustion and metabolism of glucose and amino acids.

Marina Corral Spence/Springer Nature.

Fig. 4: Integration of TCR, inhibitory and metabolic signalling.

Marina Corral Spence/Springer Nature.


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Correspondence to E. F. McKinney.

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McKinney, E.F., Smith, K.G.C. Metabolic exhaustion in infection, cancer and autoimmunity. Nat Immunol 19, 213–221 (2018).

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