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Plasmacytoid Dendritic Cells in Patients with MGUS and Multiple Myeloma

A. Knight, L. Rihova, R. Kralova, M. Penka, Z. Adam, L. Pour, M. Piskacek, R. Hajek

. 2021 ; 10 (16) : . [pub] 20210820

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc21024115

Grantová podpora
15-32935A Ministerstvo Zdravotnictví Ceské Republiky
NV19-05-00410 Ministerstvo Zdravotnictví Ceské Republiky
No.CZ.02.1.01/0.0/0.0/16_019/0000868 European Regional Development Fund-Project ENOCH

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.

Citace poskytuje Crossref.org

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$a Rihova, Lucie $u Department of Hematology, University Hospital Brno, 625 00 Brno, Czech Republic
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$a Kralova, Romana $u Department of Hematology, University Hospital Brno, 625 00 Brno, Czech Republic
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$a Penka, Miroslav $u Department of Hematology, University Hospital Brno, 625 00 Brno, Czech Republic
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$a Adam, Zdenek $u Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, 625 00 Brno, Czech Republic
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$a Pour, Ludek $u Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, 625 00 Brno, Czech Republic
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$a Piskacek, Martin $u Department of Pathological Physiology, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic
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