Kedia-Mehta, Nidhi and Tobin, Laura and Zaiatz-Bittencourt, Vanessa and Pisarska, Marta M. and De Barra, Conor and Choi, Chloe and Elamin, Einas and O’Shea, Donal and Gardiner, Clair M. and Finlay, David K. and Hogan, Andrew E. (2021) Cytokine-induced natural killer cell training is dependent on cellular metabolism and is defective in obesity. Blood Advances, 5 (21). pp. 4447-4455. ISSN 2473-9529

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Abstract

Natural killer (NK) cells are a population of innate immune cells that can rapidly kill cancer cells and produce cytokines such as interferon-γ. A key feature of NK cells is their ability to respond without prior sensitization; however, it is now well established that NK cells can possess memory-like features. After activation with cytokines, NK cells demonstrate enhanced effector functions upon restimulation days or weeks later. This demonstrates that NK cells may be trained to be more effective killers and harnessed as more potent cancer immunotherapy agents. We have previously demonstrated that cellular metabolism is essential for NK cell responses, with NK cells upregulating both glycolysis and oxidative phosphorylation upon cytokine stimulation. Limiting NK cell metabolism results in reduced cytotoxicity and cytokine production. We have also demonstrated that defective NK cell responses in obesity are linked to defective cellular metabolism. In the current study, we investigated if cellular metabolism is required during the initial period of NK cell cytokine training and if NK cells from people with obesity (PWO) can be effectively trained. We show that increased flux through glycolysis and oxidative phosphorylation during the initial cytokine activation period is essential for NK cell training, as is the metabolic signaling factor Srebp. We show that NK cells from PWO, which are metabolically defective, display impaired NK cell training, which may have implications for immunotherapy in this particularly vulnerable group.

Item Type:	Article
Additional Information:	Cite as: Nidhi Kedia-Mehta, Laura Tobin, Vanessa Zaiatz-Bittencourt, Marta M. Pisarska, Conor De Barra, Chloe Choi, Einas Elamin, Donal O’Shea, Clair M. Gardiner, David K. Finlay, Andrew E. Hogan; Cytokine-induced natural killer cell training is dependent on cellular metabolism and is defective in obesity. Blood Adv 2021; 5 (21): 4447–4455. doi: https://doi.org/10.1182/bloodadvances.2021005047
Keywords:	Immunobiology; Immunotherapy;
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Human Health Institute
Item ID:	17297
Identification Number:	https://doi.org/10.1182/bloodadvances.2021005047
Depositing User:	Andrew Hogan
Date Deposited:	08 Jun 2023 13:23
Journal or Publication Title:	Blood Advances
Publisher:	Ash publications
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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