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Leptin receptor antagonism of iNKT cell function : a novel strategy to combat multiple myeloma

Mérédis Favreau (UGent) , E Menu, Djoere Gaublomme (UGent) , K Vanderkerken, S Faict, K Maes, E De Bruyne, Srinath Govindarajan (UGent) , Michael Drennan (UGent) , Serge Van Calenbergh (UGent) , et al.
(2017) LEUKEMIA. 31(12). p.2678-2685
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Abstract
A hallmark of bone marrow changes with aging is the increase in adipocyte composition, but how this impacts development of multiple myeloma ( MM) is unknown. Here, we report the role of the adipokine leptin as master regulator of anti-myeloma tumor immunity by modulating the invariant natural killer T (iNKT) cell function. A marked increase in serum leptin levels and leptin receptor (LR) expression on iNKT cells in MM patients and the 5T33 murine MM model was observed. MM cells and leptin synergistically counteracted anti-tumor functionality of both murine and human iNKT cells. In vivo blockade of LR signaling combined with iNKT stimulation resulted in superior anti-tumor protection. This was linked to persistent IFN-gamma secretion uponrepeated iNKT cell stimulation and a restoration of the dynamic antigen-induced motility arrest as observed by intravital microscopy, thereby showing alleviation of iNKT cell anergy. Overall our data reveal the LR axis as novel therapeutic target for checkpoint inhibition to treat MM.
Keywords
KILLER T-CELLS, INVARIANT NKT CELLS, BONE-MARROW, SIGNALING PATHWAYS, ADIPOSE-TISSUE, ANERGY, ADIPOCYTES, MICROENVIRONMENT, PROGRESSION, ACTIVATION

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MLA
Favreau, Mérédis, et al. “Leptin Receptor Antagonism of INKT Cell Function : A Novel Strategy to Combat Multiple Myeloma.” LEUKEMIA, vol. 31, no. 12, 2017, pp. 2678–85, doi:10.1038/leu.2017.146.
APA
Favreau, M., Menu, E., Gaublomme, D., Vanderkerken, K., Faict, S., Maes, K., … Elewaut, D. (2017). Leptin receptor antagonism of iNKT cell function : a novel strategy to combat multiple myeloma. LEUKEMIA, 31(12), 2678–2685. https://doi.org/10.1038/leu.2017.146
Chicago author-date
Favreau, Mérédis, E Menu, Djoere Gaublomme, K Vanderkerken, S Faict, K Maes, E De Bruyne, et al. 2017. “Leptin Receptor Antagonism of INKT Cell Function : A Novel Strategy to Combat Multiple Myeloma.” LEUKEMIA 31 (12): 2678–85. https://doi.org/10.1038/leu.2017.146.
Chicago author-date (all authors)
Favreau, Mérédis, E Menu, Djoere Gaublomme, K Vanderkerken, S Faict, K Maes, E De Bruyne, Srinath Govindarajan, Michael Drennan, Serge Van Calenbergh, X Leleu, Lennart Zabeau, Jan Tavernier, Koen Venken, and Dirk Elewaut. 2017. “Leptin Receptor Antagonism of INKT Cell Function : A Novel Strategy to Combat Multiple Myeloma.” LEUKEMIA 31 (12): 2678–2685. doi:10.1038/leu.2017.146.
Vancouver
1.
Favreau M, Menu E, Gaublomme D, Vanderkerken K, Faict S, Maes K, et al. Leptin receptor antagonism of iNKT cell function : a novel strategy to combat multiple myeloma. LEUKEMIA. 2017;31(12):2678–85.
IEEE
[1]
M. Favreau et al., “Leptin receptor antagonism of iNKT cell function : a novel strategy to combat multiple myeloma,” LEUKEMIA, vol. 31, no. 12, pp. 2678–2685, 2017.
@article{8542873,
  abstract     = {{A hallmark of bone marrow changes with aging is the increase in adipocyte composition, but how this impacts development of multiple myeloma ( MM) is unknown. Here, we report the role of the adipokine leptin as master regulator of anti-myeloma tumor immunity by modulating the invariant natural killer T (iNKT) cell function. A marked increase in serum leptin levels and leptin receptor (LR) expression on iNKT cells in MM patients and the 5T33 murine MM model was observed. MM cells and leptin synergistically counteracted anti-tumor functionality of both murine and human iNKT cells. In vivo blockade of LR signaling combined with iNKT stimulation resulted in superior anti-tumor protection. This was linked to persistent IFN-gamma secretion uponrepeated iNKT cell stimulation and a restoration of the dynamic antigen-induced motility arrest as observed by intravital microscopy, thereby showing alleviation of iNKT cell anergy. Overall our data reveal the LR axis as novel therapeutic target for checkpoint inhibition to treat MM.}},
  author       = {{Favreau, Mérédis and Menu, E and Gaublomme, Djoere and Vanderkerken, K and Faict, S and Maes, K and De Bruyne, E and Govindarajan, Srinath and Drennan, Michael and Van Calenbergh, Serge and Leleu, X and Zabeau, Lennart and Tavernier, Jan and Venken, Koen and Elewaut, Dirk}},
  issn         = {{0887-6924}},
  journal      = {{LEUKEMIA}},
  keywords     = {{KILLER T-CELLS,INVARIANT NKT CELLS,BONE-MARROW,SIGNALING PATHWAYS,ADIPOSE-TISSUE,ANERGY,ADIPOCYTES,MICROENVIRONMENT,PROGRESSION,ACTIVATION}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{2678--2685}},
  title        = {{Leptin receptor antagonism of iNKT cell function : a novel strategy to combat multiple myeloma}},
  url          = {{http://doi.org/10.1038/leu.2017.146}},
  volume       = {{31}},
  year         = {{2017}},
}
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