J 2021

Plasmacytoid Dendritic Cells in Patients with MGUS and Multiple Myeloma

KNIGHT, Andrea, Lucie ŘÍHOVÁ, Romana KRÁLOVÁ, Miroslav PENKA, Zdeněk ADAM et. al.

Basic information

Original name

Plasmacytoid Dendritic Cells in Patients with MGUS and Multiple Myeloma

Authors

KNIGHT, Andrea (203 Czech Republic, guarantor, belonging to the institution), Lucie ŘÍHOVÁ (203 Czech Republic), Romana KRÁLOVÁ (203 Czech Republic), Miroslav PENKA (203 Czech Republic), Zdeněk ADAM (203 Czech Republic), Luděk POUR (203 Czech Republic), Martin PISKÁČEK (40 Austria, belonging to the institution) and Roman HAJEK (203 Czech Republic)

Edition

Journal of Clinical Medicine, Basel, MDPI, 2021, 2077-0383

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30218 General and internal medicine

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 4.964

RIV identification code

RIV/00216224:14110/21:00120139

Organization unit

Faculty of Medicine

UT WoS

000689192700001

Keywords in English

plasmacytoid dendritic cells; MGUS; multiple myeloma; immunosuppressive tumor microenvironment

Tags

Tags

International impact, Reviewed
Změněno: 9/9/2021 06:57, Mgr. Tereza Miškechová

Abstract

V originále

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.

Links

NV15-32935A, research and development project
Name: Analýza gamma-delta T lymfocytů reaktivních na nádorové buňky u pacientů s B-buněčnou chronickou lymfocytární leukémií: nový přístup k buněčné terapii
NV19-05-00410, research and development project
Name: Úloha cytotoxických gamma-delta T buněk na terapeutické rezistenci a recidivě Glioblastoma Multiforme
Investor: Ministry of Health of the CR