Abstract:
:Natural killer (NK) cells play critical roles in protection against hematological malignancies but can acquire a dysfunctional state, which limits antitumor 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 peroxisome activator receptor-γ (PPAR-γ). 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 Eµ-myc B-cell lymphoma-bearing mice displayed reduced interferon-γ (IFN-γ) production. Activation of PPAR-γ partially restored mitochondrial membrane potential and IFN-γ 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.
journal_name
Bloodjournal_title
Bloodauthors
Kobayashi T,Lam PY,Jiang H,Bednarska K,Gloury R,Murigneux V,Tay J,Jacquelot N,Li R,Tuong ZK,Leggatt GR,Gandhi MK,Hill MM,Belz GT,Ngo S,Kallies A,Mattarollo SRdoi
10.1182/blood.2020005602subject
Has Abstractpub_date
2020-12-24 00:00:00pages
3004-3017issue
26eissn
0006-4971issn
1528-0020pii
463339journal_volume
136pub_type
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