Cancer Immunology, Immunotherapy

, Volume 64, Issue 2, pp 213–224 | Cite as

Immune impairments in multiple myeloma bone marrow mesenchymal stromal cells

  • Thibaud AndréEmail author
  • Mehdi Najar
  • Basile Stamatopoulos
  • Karlien Pieters
  • Olivier Pradier
  • Dominique Bron
  • Nathalie Meuleman
  • Laurence Lagneaux
Original Article


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.


MSCs Myeloma Immunomodulation Th17/Treg 



Bone marrow




Chemokine (C–C motif) ligand 5


Carboxyfluorescein succinimidyl ester


Conditioned medium


Enzyme-linked immunosorbent assay


Forkhead box P3


Healthy donors


Hepatocyte growth factor


Human leukocyte antigen




Intercellular adhesion molecule-1






Interleukin-23 receptor


Lymphocyte function-associated antigen-3


Monocyte chemotactic protein-1


Macrophage inflammatory protein-1 alpha


Mixed lymphocyte reactions


Multiple myeloma


Matrix metalloproteinase


Mesenchymal stromal cell


Peripheral blood mononuclear cells


Plasma cells


Prostaglandin E2




RAR-related orphan receptor gamma t


Standard error of the mean


Tumor growth factor


T helper cells


Tumor necrosis factor


T regulatory cells


Vascular cell adhesion molecule-1



This work was supported by a Grant provided by the “Fonds de la Recherche Scientifique—Fonds National de la Recherche Scientifique” (FRS-FNRS of Belgium—Grant-Télévie FC79946) and by a fund Granted by “Les Amis de l’Institut Bordet.”

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

262_2014_1623_MOESM1_ESM.pdf (105 kb)
Supplementary material 1 (PDF 105 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Thibaud André
    • 1
    Email author
  • Mehdi Najar
    • 1
  • Basile Stamatopoulos
    • 1
  • Karlien Pieters
    • 1
  • Olivier Pradier
    • 3
  • Dominique Bron
    • 2
  • Nathalie Meuleman
    • 2
  • Laurence Lagneaux
    • 1
  1. 1.Laboratory of Clinical Cell TherapyInstitut Jules Bordet - Université Libre de Bruxelles (ULB)BrusselsBelgium
  2. 2.Hematology DepartmentInstitut Jules BordetBrusselsBelgium
  3. 3.Laboratory of HematologyErasmus HospitalBrusselsBelgium

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