Increased lipid metabolism impairs NK cell function and mediates adaptation to the lymphoma environment
| Autor: | Zewen K. Tuong, Renee Gloury, Graham R. Leggatt, Takumi Kobayashi, Valentine Murigneux, Maher K. Gandhi, Rui Li, Axel Kallies, Karolina Bednarska, Stephen R. Mattarollo, Joshua Tay, Shyuan T. Ngo, Gabrielle T. Belz, Hui Jiang, Michelle M. Hill, Pui Yeng Lam, Nicolas Jacquelot |
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| Rok vydání: | 2020 |
| Předmět: |
Immunology
Cell Peroxisome proliferator-activated receptor Mice Transgenic Biology Biochemistry Interferon-gamma Mice Interferon medicine Tumor Microenvironment Animals Humans Interferon gamma Receptor chemistry.chemical_classification Membrane Potential Mitochondrial Tumor microenvironment Lipid metabolism Cell Biology Hematology Lipid Metabolism Neoplasm Proteins Killer Cells Natural PPAR gamma medicine.anatomical_structure chemistry Apoptosis Cancer research Lymphoma Large B-Cell Diffuse medicine.drug |
| Zdroj: | Blood. 136(26) |
| ISSN: | 1528-0020 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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