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Assessing the Development of Murine Plasmacytoid Dendritic Cells in Peyer's Patches Using Adoptive Transfer of Hematopoietic Progenitors
Published on: March 17, 2014
Plasmacytoid Dendritic Cells in Patients with MGUS and Multiple Myeloma
Andrea Knight1, Lucie Rihova2, Romana Kralova2
1Department of Pathological Physiology, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic.
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 IFNα 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 IFNα 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.
Insights
Plasmacytoid dendritic cells (pDCs) are reduced in multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). These pDCs promote MM cell proliferation and secrete IFNα, suggesting a role in immune suppression.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- Plasmacytoid dendritic cells (pDCs) are key immune mediators.
- Their role in the immunosuppressive tumor microenvironment of multiple myeloma (MM) is not well understood.
Purpose of the Study:
- To investigate pDC frequencies in MM and related conditions.
- To determine the functional role of pDCs in MM tumor cell proliferation and immune signaling.
Main Methods:
- Flow cytometry was used to quantify pDC counts in newly diagnosed MM patients, monoclonal gammopathy of undetermined significance (MGUS) patients, and healthy donors.
- In vitro co-culture experiments assessed myeloma tumor cell proliferation and IFNα production by pDCs.
Main Results:
- A significant reduction in pDCs was observed in both the blood and bone marrow of MM patients compared to healthy donors.
- pDC counts were also decreased in the bone marrow of MGUS patients.
- pDCs were found to specifically promote MM cell proliferation and secrete IFNα upon co-culture with MM cells.
Conclusions:
- Altered pDC frequencies are present in the bone marrow microenvironment of MGUS and MM patients at diagnosis.
- pDCs exhibit tumor-promoting functions in MM, potentially contributing to immune deficiencies and impacting disease control and treatment outcomes.
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