title: Immune impairments in multiple myeloma bone marrow mesenchymal stromal cells.
abstract: In multiple myeloma (MM), bone marrow mesenchymal stromal cells (BM-MSCs) play an important role in pathogenesis and disease progression by supporting myeloma cell growth and immune escape. Previous studies have suggested that direct and indirect interactions between malignant cells and BM-MSCs result in constitutive abnormal immunomodulatory capacities in MM BM-MSCs. The aim of this study was to investigate the mechanisms that underlie these MM BM-MSCs abnormalities. We demonstrated that MM BM-MSCs exhibit abnormal expression of CD40/40L, VCAM1, ICAM-1, LFA-3, HO-1, HLA-DR and HLA-ABC. Furthermore, an overproduction of IL-6 (1,806 ± 152.5 vs 719.6 ± 18.22 ng/mL; p = 0.035) and a reduced secretion of IL-10 (136 ± 15.02 vs 346.4 ± 35.32 ng/mL; p = 0.015) were quantified in culture medium when MM BM-MSCs were co-cultured with T lymphocytes compared to co-cultures with healthy donor (HD) BM-MSCs. An increased Th17/Treg ratio was observed when T cells were co-cultured with MM BM-MSCs compared to co-cultures with HD BM-MSCs (0.955 vs 0.055). Together, these observations demonstrated that altered immunomodulation capacities of MM BM-MSCs were linked to variations in their immunogenicity and secretion profile. These alterations lead not only to a reduced inhibition of T cell proliferation but also to a shift in the Th17/Treg balance. We identified factors that are potentially responsible for these alterations, such as IL-6, VCAM-1 and CD40, which could also be associated with MM pathogenesis and progression.
authors.affiliation: Laboratory of Clinical Cell Therapy, Institut Jules Bordet - Université Libre de Bruxelles (ULB), 808, Route de Lennik, 1070, Brussels, Belgium, thibaud.andre@bordet.be.
authors.forename: Thibaud
authors.initials: T
authors.lastname: André
authors.forename: Mehdi
authors.initials: M
authors.lastname: Najar
authors.forename: Basile
authors.initials: B
authors.lastname: Stamatopoulos
authors.forename: Karlien
authors.initials: K
authors.lastname: Pieters
authors.forename: Olivier
authors.initials: O
authors.lastname: Pradier
authors.forename: Dominique
authors.initials: D
authors.lastname: Bron
authors.forename: Nathalie
authors.initials: N
authors.lastname: Meuleman
authors.forename: Laurence
authors.initials: L
authors.lastname: Lagneaux
mesh_terms: D019013:CD40 Antigens / Q000378:metabolism; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D009101:Multiple Myeloma / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D019013:CD40 Antigens; D016207:Cytokines; D018836:Inflammation Mediators; D019010:Vascular Cell Adhesion Molecule-1