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

被引：0
|
作者：
M Favreau
E Menu
D Gaublomme
K Vanderkerken
S Faict
K Maes
E De Bruyne
S Govindarajan
M Drennan
S Van Calenbergh
X Leleu
L Zabeau
J Tavernier
K Venken
D Elewaut
机构：
[1] Myeloma Center Brussels,Department of Hematology and Immunology
[2] Vrije Universiteit Brussel,Department of Rheumatology
[3] Ghent University Hospital,Department of Pharmaceutics
[4] Unit for Molecular Immunology and Inflammation,Department of Biochemistry
[5] VIB Inflammation Research Center,undefined
[6] Ghent University,undefined
[7] Laboratory for Medicinal Chemistry,undefined
[8] Faculty of Pharmaceutical Sciences,undefined
[9] Ghent University,undefined
[10] Service d’Hématologie et Thérapie Cellulaire,undefined
[11] Pôle Régional de Cancérologie,undefined
[12] Hospital de la Miléterie,undefined
[13] VIB Medical Biotechnology Center,undefined
[14] Faculty of Medicine and Health Sciences,undefined
[15] Ghent University,undefined
来源：
Leukemia | 2017年 / 31卷
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摘要：
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-γ secretion upon repeated 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.
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页码：2678 / 2685
页数：7
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