Impaired functionality and phenotypic profile of dendritic cells from patients with multiple myeloma.
Multiple myeloma (MM) is a B cell cancer characterized by clonal proliferation in the bone marrow and impaired immunity. Because MM is an incurable malignancy, efficient consolidation is needed urgently. Targeting clonotypic B cells by idiotype vaccination has proved the principle to be effective and indicated that future strategies, including dendritic cell-based vaccination, could be a suitable approach. However, as MM patients suffer from a general impaired immunity, which may include dendritic cells (DCs), a careful evaluation of phenotypic traits and functionality of DCs from MM patients is necessary before an efficient vaccine can be developed. This study determined the number, phenotypic profile and functionality of myeloid and plasmacytoid DCs purified directly from blood from MM patients at diagnosis. A reduced number and lower expression of human leucocyte antigen (HLA) molecules was observed on both myeloid and plasmacytoid DCs in MM patients compared to healthy controls. Also, the expression of CCR5, CCR7 and DEC205 was lower in MM patients compared to normal donors. In addition, the capacity to stimulate allogeneic T cell proliferation and to stimulate cytokine production was decreased, suggesting that DCs from these patients are functionally impaired. Finally, the analysis of samples following chemotherapy and transplantation demonstrated an increased expression of HLA molecules, suggesting that this time-point is optimal for harvest and use in vaccination.
Department of Haematology, Herlev Hospital, Herlev Ringvej, University of Copenhagen, Herlev, Denmark. mbrimnes@hotmail.com
M K
MK
Brimnes
I M
IM
Svane
H E
HE
Johnsen
D015703:Antigens, CD / Q000032:analysis; D002452:Cell Count; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D037181:Lectins, C-Type / Q000032:analysis; D015778:Minor Histocompatibility Antigens; D009101:Multiple Myeloma / Q000097:blood / Q000276:immunology* / Q000628:therapy; D022423:Myeloid Cells / Q000276:immunology; D010641:Phenotype; D019713:Receptors, CCR5 / Q000032:analysis; D054400:Receptors, CCR7; D011956:Receptors, Cell Surface / Q000032:analysis; D019707:Receptors, Chemokine / Q000032:analysis; D033581:Stem Cell Transplantation / Q000379:methods; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; C515370:CCR7 protein, human; D016207:Cytokines; C093569:DEC-205 receptor; D006680:HLA Antigens; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D019713:Receptors, CCR5; D054400:Receptors, CCR7; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine