Increased lipid metabolism impairs NK cell function and mediates adaptation to the lymphoma environment
- Author(s)
- Kobayashi, T; Lam, PY; Jiang, H; Bednarska, K; Gloury, RE; Murigneux, V; Tay, J; Jacquelot, N; Li, R; Tuong, ZK; Leggatt, G; Gandhi, MK; Hill, MM; Belz, GT; Ngo, S; Kallies, A; Mattarollo, SR;
- Journal Title
- Blood
- Publication Type
- Journal epub ahead of print
- Abstract
- NK cells play critical roles in protection against haematological malignancies but can acquire a dysfunctional state, which limits anti-tumour immunity. However, the underlying reasons for this impaired NK cell function remain to be uncovered. We found that NK cells in aggressive B cell lymphoma underwent substantial transcriptional reprogramming associated with increased lipid metabolism, including elevated expression of the transcriptional regulator PPAR-g. Exposure to fatty acids in the lymphoma environment potently suppressed NK cell effector response and cellular metabolism. NK cells from both diffuse large B cell lymphoma patients and Emicro-myc B cell lymphoma-bearing mice displayed reduced IFN-g production. Activation of PPAR-g partially restored mitochondrial membrane potential and IFN-g production. Overall our data indicate that increased lipid metabolism, while impairing their function, is a functional adaptation of NK cells to the fatty-acid rich lymphoma environment.
- Publisher
- ASH
- Research Division(s)
- Immunology
- PubMed ID
- 32818230
- Publisher's Version
- https://doi.org/10.1182/blood.2020005602
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2020-10-02 09:53:38
Last Modified: 2020-10-02 10:12:18