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Leptin receptor antagonism of iNKT cell function : a novel strategy to combat multiple myeloma. / Favreau, M; Menu, Eline; Gaublomme, D; Vanderkerken, K; Faict, S; Maes, Ken; De Bruyne, E; Govindarajan, S; Drennan, M; Van Calenbergh, S; Leleu, Xavier; Zabeau, L; Tavernier, Jan; Venken, Koen; Elewaut, Dirk.

In: Leukemia, Vol. 31, No. 12, 12.2017, p. 2678-2685.

Research output: Contribution to journalArticle

Harvard

Favreau, M, Menu, E, Gaublomme, D, Vanderkerken, K, Faict, S, Maes, K, De Bruyne, E, Govindarajan, S, Drennan, M, Van Calenbergh, S, Leleu, X, Zabeau, L, Tavernier, J, Venken, K & Elewaut, D 2017, 'Leptin receptor antagonism of iNKT cell function: a novel strategy to combat multiple myeloma', Leukemia, vol. 31, no. 12, pp. 2678-2685. https://doi.org/10.1038/leu.2017.146

APA

Vancouver

Author

Favreau, M ; Menu, Eline ; Gaublomme, D ; Vanderkerken, K ; Faict, S ; Maes, Ken ; De Bruyne, E ; Govindarajan, S ; Drennan, M ; Van Calenbergh, S ; Leleu, Xavier ; Zabeau, L ; Tavernier, Jan ; Venken, Koen ; Elewaut, Dirk. / Leptin receptor antagonism of iNKT cell function : a novel strategy to combat multiple myeloma. In: Leukemia. 2017 ; Vol. 31, No. 12. pp. 2678-2685.

BibTeX

@article{baed40841bee44b09edda0b4cd9e34f9,
title = "Leptin receptor antagonism of iNKT cell function: a novel strategy to combat multiple myeloma",
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-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.Leukemia advance online publication, 16 June 2017; doi:10.1038/leu.2017.146.",
keywords = "Animals, Antibodies, Monoclonal, Antineoplastic Agents/pharmacology, Cell Line, Tumor, Cell Proliferation/drug effects, Cytokines/biosynthesis, Disease Models, Animal, Galactosylceramides/pharmacology, Humans, Leptin/metabolism, Lymphocyte Activation/drug effects, Mice, Mice, Knockout, Molecular Targeted Therapy, Multiple Myeloma/drug therapy, Natural Killer T-Cells/drug effects, Receptors, Leptin/antagonists & inhibitors, Xenograft Model Antitumor Assays",
author = "M Favreau and Eline Menu and D Gaublomme and K Vanderkerken and S Faict and Ken Maes and {De Bruyne}, E and S Govindarajan and M Drennan and {Van Calenbergh}, S and Xavier Leleu and L Zabeau and Jan Tavernier and Koen Venken and Dirk Elewaut",
year = "2017",
month = "12",
doi = "10.1038/leu.2017.146",
language = "English",
volume = "31",
pages = "2678--2685",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "12",

}

RIS

TY - JOUR

T1 - Leptin receptor antagonism of iNKT cell function

T2 - a novel strategy to combat multiple myeloma

AU - Favreau, M

AU - Menu, Eline

AU - Gaublomme, D

AU - Vanderkerken, K

AU - Faict, S

AU - Maes, Ken

AU - De Bruyne, E

AU - Govindarajan, S

AU - Drennan, M

AU - Van Calenbergh, S

AU - Leleu, Xavier

AU - Zabeau, L

AU - Tavernier, Jan

AU - Venken, Koen

AU - Elewaut, Dirk

PY - 2017/12

Y1 - 2017/12

N2 - 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.Leukemia advance online publication, 16 June 2017; doi:10.1038/leu.2017.146.

AB - 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.Leukemia advance online publication, 16 June 2017; doi:10.1038/leu.2017.146.

KW - Animals

KW - Antibodies, Monoclonal

KW - Antineoplastic Agents/pharmacology

KW - Cell Line, Tumor

KW - Cell Proliferation/drug effects

KW - Cytokines/biosynthesis

KW - Disease Models, Animal

KW - Galactosylceramides/pharmacology

KW - Humans

KW - Leptin/metabolism

KW - Lymphocyte Activation/drug effects

KW - Mice

KW - Mice, Knockout

KW - Molecular Targeted Therapy

KW - Multiple Myeloma/drug therapy

KW - Natural Killer T-Cells/drug effects

KW - Receptors, Leptin/antagonists & inhibitors

KW - Xenograft Model Antitumor Assays

UR - http://www.scopus.com/inward/record.url?scp=85038234298&partnerID=8YFLogxK

U2 - 10.1038/leu.2017.146

DO - 10.1038/leu.2017.146

M3 - Article

C2 - 28490813

VL - 31

SP - 2678

EP - 2685

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 12

ER -

ID: 34911108