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Leptin receptor antagonism of iNKT cell function: a novel strategy to combat multiple myeloma.
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.
Afiliación
  • Favreau M; Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
  • Menu E; Department of Rheumatology, Ghent University Hospital, Ghent, Belgium.
  • Gaublomme D; Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center, Ghent University, Ghent, Belgium.
  • Vanderkerken K; Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
  • Faict S; Department of Rheumatology, Ghent University Hospital, Ghent, Belgium.
  • Maes K; Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center, Ghent University, Ghent, Belgium.
  • De Bruyne E; Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
  • Govindarajan S; Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
  • Drennan M; Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
  • Van Calenbergh S; Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
  • Leleu X; Department of Rheumatology, Ghent University Hospital, Ghent, Belgium.
  • Zabeau L; Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center, Ghent University, Ghent, Belgium.
  • Tavernier J; Department of Rheumatology, Ghent University Hospital, Ghent, Belgium.
  • Venken K; Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center, Ghent University, Ghent, Belgium.
  • Elewaut D; Laboratory for Medicinal Chemistry, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
Leukemia ; 31(12): 2678-2685, 2017 12.
Article en En | MEDLINE | ID: mdl-28490813
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Leptina / Células T Asesinas Naturales / Mieloma Múltiple / Antineoplásicos Límite: Animals / Humans Idioma: En Revista: Leukemia Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2017 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Leptina / Células T Asesinas Naturales / Mieloma Múltiple / Antineoplásicos Límite: Animals / Humans Idioma: En Revista: Leukemia Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2017 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Reino Unido