Immunometabolism and natural killer cell responses

Abstract

Natural killer (NK) cells are lymphocytes with important roles in innate and adaptive immune responses to tumours and viral infection. However, in certain chronic diseases, including obesity and cancer, NK cell functional responses are impaired. Recently, research has highlighted the importance of NK cell metabolism in facilitating robust NK cell effector functions. This Review describes our current understanding of mouse and human NK cell metabolism and the key signalling pathways that mediate metabolic responses in NK cells. Furthermore, it explores how defects in metabolism can contribute to the generation of dysfunctional NK cells in chronic disease. Finally, the potential for new therapeutic strategies targeting cellular metabolism is discussed.

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Fig. 1: The citrate–malate shuttle.
Fig. 2: Key regulators of NK cell metabolism.
Fig. 3: Mechanisms disrupting NK cell metabolism in cancer and obesity.

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Acknowledgements

The authors acknowledge funding from the following sources: European Commission (EU Framework Programme for Research and Innovation H2020, H2020 Priority Excellent Science and H2020 European Research Council) and Science Foundation Ireland to D.K.F. and Irish Cancer Society to K.L.O’B.

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Nature Reviews Immunology thanks J. Miller and other anonymous reviewer(s) for their contribution to the peer review of this work.

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Correspondence to David K. Finlay.

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O’Brien, K.L., Finlay, D.K. Immunometabolism and natural killer cell responses. Nat Rev Immunol 19, 282–290 (2019). https://doi.org/10.1038/s41577-019-0139-2

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