Increased Lipid Metabolism Impairs Nk Cell Function And Mediates Adaptation To The Lymphoma Environment
BLOOD(2020)
摘要
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-gamma (PPAR-gamma). 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 E mu-myc B-cell lymphoma-bearing mice displayed reduced interferon-gamma (IFN-gamma) production. Activation of PPAR-gamma partially restored mitochondrialmembrane potential and IFN-gamma 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.
更多查看译文
关键词
nk cell function,lymphoma environment,lipid metabolism
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要