期刊
BLOOD
卷 136, 期 26, 页码 3004-3017出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood.2020005602
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资金
- National Health and Medical Research Council [1044355, 1061429, 1139607]
- Sylvia and Charles Viertel Foundation fellowship
- National Health and Medical Research Council of Australia [1061429, 1139607] Funding Source: NHMRC
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.
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