Publication details

Plasmacytoid Dendritic Cells in Patients with MGUS and Multiple Myeloma


KNIGHT Andrea ŘÍHOVÁ Lucie KRÁLOVÁ Romana PENKA Miroslav ADAM Zdeněk POUR Luděk PISKÁČEK Martin HAJEK Roman

Year of publication 2021
Type Article in Periodical
Magazine / Source Journal of Clinical Medicine
MU Faculty or unit

Faculty of Medicine

Keywords plasmacytoid dendritic cells; MGUS; multiple myeloma; immunosuppressive tumor microenvironment
Description Background: Plasmacytoid dendritic cells (pDCs) play prominent roles in mediating innate and adaptive immune responses. However, it is unclear how pDCs contribute to the immunosuppressive tumor microenvironment described in multiple myeloma (MM). Methods: Newly diagnosed myeloma patients (MM, n = 37) were analyzed to determine the pDC counts in comparison to peripheral blood (PB, n = 53) and bone marrow (BM, n = 10) samples of age-matched healthy donors (HD) using flow cytometry. Second, proliferation of myeloma tumor cells in the presence of freshly isolated pDCs was examined. Third, production of IFN alpha by pDCs co-cultured with MM cells was determined by intracellular staining. Results: We found a highly significant reduction of circulating pDCs (p < 0.0001) and in bone marrow (p < 0.0001) of MM patients compared to HD. We also observed a significant decrease of pDCs (p = 0.004) in BM in patients with monoclonal gammopathy of undetermined significance (MGUS, n = 12). Importantly, we determined that pDCs promote proliferation specifically of MM cells and not the stromal cells and that pDCs secrete IFN alpha upon co-culture with MM tumor cells. Conclusions: Our results show altered pDC frequencies in the BM microenvironment in MGUS and MM patients at diagnosis. We showed the tumor-promoting function of pDCs that may mediate immune deficiencies affecting long-term disease control and treatment outcome.
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