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Multiple Myeloma, Gammopathies

Autologous bone marrow Th cells can support multiple myeloma cell proliferation in vitro and in xenografted mice

Leukemia volume 31, pages 2114–2121 (2017)Cite this article

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Abstract

Multiple myeloma (MM) is a plasma cell malignancy where MM cell growth is supported by the bone marrow (BM) microenvironment with poorly defined cellular and molecular mechanisms. MM cells express CD40, a receptor known to activate autocrine secretion of cytokines and elicit proliferation. Activated T helper (Th) cells express CD40 ligand (CD40L) and BM Th cells are significantly increased in MM patients. We hypothesized that activated BM Th cells could support MM cell growth. We here found that activated autologous BM Th cells supported MM cell growth in a contact- and CD40L-dependent manner in vitro. MM cells had retained the ability to activate Th cells that reciprocated and stimulated MM cell proliferation. Autologous BM Th cells supported MM cell growth in xenografted mice and were found in close contact with MM cells. MM cells secreted chemokines that attracted Th cells, secretion was augmented by CD40-stimulation. Within 14 days of culture of whole BM aspirates in autologous serum, MM cells and Th cells mutually stimulated each other, and MM cells required Th cells for further expansion in vitro and in mice. The results suggest that Th cells may support the expansion of MM cells in patients.

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Acknowledgements

This work was supported by grants from the Norwegian South-East Health region to LAM, the Research Council of Norway through its Centres of Excellence funding scheme (Project Number 179573/V40) to LAM, the Torsteds fund, the Raagholt fund and Unifor to DW.

Author contributions

DW, YF, CM, POH, SB, AP-R, AT and LAM performed experiments. JD, YF, FS and GET provided patient samples and clinical information. DW, YF, CM, SB, AP-R, POH, BB, AT and LAM analyzed data. All co-authors contributed to data interpretation, manuscript preparation. DW and LAM designed the research and wrote the paper.

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Author notes

  1. S Bürgler

    Present address: 7Current address: Swiss Experimental Infectious Diseases and Cancer Research, University Children's Hospital, CH-8008 Zürich, Switzerland.,

  2. A Tveita and L A Munthe: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, Centre for Immune Regulation, Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    D Wang, C V Myklebust, S Bürgler, A Parente-Ribes, P O Hofgaard, B Bogen, F Schjesvold, A Tveita & L A Munthe

  2. Department of Haematology, Oslo University Hospital, Oslo, Norway

    Y Fløisand, S Bürgler, G E Tjønnfjord, F Schjesvold & J Dalgaard

  3. KG Jebsen Centre for Influenza Vaccine Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    P O Hofgaard & B Bogen

  4. Centre for Molecular Medicine Norway (NCMM), University of Oslo, Oslo, Norway

    K Taskén

  5. Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    G E Tjønnfjord

  6. Department of Medicine, Vestre Viken Trust, Drammen Hospital, Drammen, Norway

    J Dalgaard

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Correspondence to D Wang, A Tveita or L A Munthe.

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Wang, D., Fløisand, Y., Myklebust, C. et al. Autologous bone marrow Th cells can support multiple myeloma cell proliferation in vitro and in xenografted mice. Leukemia 31, 2114–2121 (2017). https://doi.org/10.1038/leu.2017.69

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