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

(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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Chicago
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): 2678–2685.
APA
Favreau, M., Menu, E., Gaublomme, D., Vanderkerken, K., Faict, S., Maes, K., De Bruyne, E., et al. (2017). Leptin receptor antagonism of iNKT cell function : a novel strategy to combat multiple myeloma. LEUKEMIA, 31(12), 2678–2685.
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.
MLA
Favreau, Mérédis, E Menu, Djoere Gaublomme, et al. “Leptin Receptor Antagonism of iNKT Cell Function : a Novel Strategy to Combat Multiple Myeloma.” LEUKEMIA 31.12 (2017): 2678–2685. Print.
@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, M{\'e}r{\'e}dis 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},
  language     = {eng},
  number       = {12},
  pages        = {2678--2685},
  title        = {Leptin receptor antagonism of iNKT cell function : a novel strategy to combat multiple myeloma},
  url          = {http://dx.doi.org/10.1038/leu.2017.146},
  volume       = {31},
  year         = {2017},
}

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