title: Preclinical evaluation of invariant natural killer T cells in the 5T33 multiple myeloma model.
abstract: Immunomodulators have been used in recent years to reactivate host anti-tumor immunity in several hematological malignancies. This report describes the effect of activating natural killer T (NKT) cells by α-Galactosylceramide (α-GalCer) in the 5T33MM model of multiple myeloma (MM). NKT cells are T lymphocytes, co-expressing T and NK receptors, while invariant NKT cells (iNKTs) also express a unique semi-invariant TCR α-chain. We followed iNKT numbers during the development of the disease in both 5T33MM mice and MM patients and found that their numbers dropped dramatically at the end stage of the disease, leading to a loss of total IFN-γ secretion. We furthermore observed that α-GalCer treatment significantly increased the survival of 5T33MM diseased mice. Taken together, our data demonstrate for the first time the possibility of using a preclinical murine MM model to study the effects of α-GalCer and show promising results of α-GalCer treatment in a low tumor burden setting.
authors.affiliation: Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
authors.forename: Haneen
authors.initials: H
authors.lastname: Nur
authors.forename: Karel
authors.initials: K
authors.lastname: Fostier
authors.forename: Sandrine
authors.initials: S
authors.lastname: Aspeslagh
authors.forename: Wim
authors.initials: W
authors.lastname: Renmans
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bertrand
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
authors.forename: Mérédis
authors.initials: M
authors.lastname: Favreau
authors.forename: Karine
authors.initials: K
authors.lastname: Breckpot
authors.forename: Rik
authors.initials: R
authors.lastname: Schots
authors.forename: Marc
authors.initials: M
authors.lastname: De Waele
authors.forename: Els
authors.initials: E
authors.lastname: Van Valckenborgh
authors.forename: Elke
authors.initials: E
authors.lastname: De Bruyne
authors.forename: Thierry
authors.initials: T
authors.lastname: Facon
authors.forename: Dirk
authors.initials: D
authors.lastname: Elewaut
authors.forename: Karin
authors.initials: K
authors.lastname: Vanderkerken
authors.forename: Eline
authors.initials: E
authors.lastname: Menu
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000378:metabolism; D004195:Disease Models, Animal; D005699:Galactosylceramides / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018655:Lymphocyte Count; D051379:Mice; D009101:Multiple Myeloma / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: D055610:Antigens, CD1d; D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D007371:Interferon-gamma