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Enhancement of myeloma development mediated though myeloma cell-Th2 cell interactions after microbial antigen

F Tian, J Li, Y Li

    Blood Cancer Journal
    |July 26, 2012
    PubMed

    Insights

    Microbes and microbial antigens can directly impact myeloma progression. Bacillus Calmette-Guerin Vaccine-specific Th2 cells promote myeloma growth by upregulating HLA-DR and CD40, suggesting new therapeutic targets.

    Area of Science:

    • Immunology
    • Oncology
    • Microbiology

    Background:

    • Microbial agents are potential carcinogens, but their direct role in myeloma tumor biology is unclear.
    • Previous research has not established a direct link between Th2 cells and myeloma growth promotion.

    Purpose of the Study:

    • To investigate the direct effects of microbial antigens and microbial-specific T helper 2 (Th2) cells on myeloma cells.
    • To explore the mechanisms by which microbial factors influence myeloma progression and identify potential therapeutic targets.

    Main Methods:

    • Upregulation of HLA-DR and CD40 on myeloma cells by interferon-γ and microbial antigens.
    • Stimulation of Bacillus Calmette-Guerin Vaccine (BCGV)-specific Th2 cells using BCGV-loaded dendritic cells (DCs).
    • Assessment of myeloma clonogenicity, B-cell lymphoma 6 (Bcl-6) protein expression, and cell surface marker proportions in Th2 cell-stimulated myeloma cells.

    Main Results:

    • BCGV-specific Th2 cells directly promoted myeloma clonogenicity in MHC-II(+) myeloma cells that took up BCGV antigen.
    • Th2 cell stimulation led to increased Bcl-6 protein expression and a higher proportion of HLA-DR(+) or CD40(+) myeloma cells.
    • Blocking HLA-DR or CD40 with antibodies inhibited the increase in Bcl-6 expression and colony number.

    Conclusions:

    • Microbes and microbial antigen-specific Th2 cells can directly influence myeloma biology and promote tumor progression.
    • Activation appears specific to MHC-II(+) myeloma cells with B cell and stem cell characteristics.
    • Dendritic cells and Th2 cells involved in microbial antigen presentation are potential targets for myeloma therapy.
    Keywords:
    Th2 cellantigen presentationclonogenicitydendritic cellmicrobial antigenmyeloma

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