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Increased lipid metabolism impairs NK cell function and mediates adaptation to the lymphoma environment


  • Kobayashi, Takumi
  • Lam, Pui Yeng
  • Jiang, Hui
  • Bednarska, Karolina
  • Gloury, Renee
  • Murigneux, Valentine
  • Tay, Joshua
  • Jacquelot, Nicolas
  • Li, Rui
  • Tuong, Zewen Kelvin
  • Leggatt, Graham R.
  • Gandhi, Maher K.
  • Hill, Michelle M.
  • Belz, Gabrielle T.
  • Ngo, Shyuan
  • Kallies, Axel
  • Mattarollo, Stephen R.


Blood, Volume 136, Issue 26, 2020-12-24

Article Link: Click here

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.