Dendritic cells generated from the blood of patients with multiple myeloma are phenotypically and functionally identical to those similarly produced from healthy donors

Abstract

Summary. Using a combination of GM-CSF, SCF, flk-2/flt-3 ligand, and IL-4, dendritic cells (DC) have been generated in vitro from the adherent fraction of mononuclear cells isolated from the blood of patients with MM. Analysis of cell yield showed no significant difference in DC yield (numbers or percentage of leucocytes) or total number of leucocytes generated in myeloma cultures compared to similar cultures prepared using mononuclear cells from the blood of healthy donors. The mean number of DC produced after 10 d of culture were 8 . 19 × 10 5 and 9 . 87 × 10 5 cells (41% and 51% of all leucocytes) for the myeloma and normal cultures respectively. Flow cytometry investigation of phenotypic markers including CD1a, HLA-DR, CD80 (BB1/B7.1) and CD86 (B70/B7.2), and functional status (stimulatory potential in allogeneic mixed leucocyte reactions (MLR)) confirmed the generation of cells phenotypically identified as cultured DC. In addition, these cells were more effective than PBMC at stimulating allogeneic PBMC proliferation. These data demonstrate no difference between DC generated from patients with MM and healthy donors. This study was considered a prerequisite for future investigations directed towards developing effective immunotherapies for myeloma.

Peripheral Blood Dendritic Cell Subsets from Patients with Monoclonal Gammopathies Show an Abnormal Distribution and Are Functionally Impaired

“…Accordingly, while some studies have shown the presence of lower numbers of circulating mDCs [35] or both mDCs and pDCs in MM patients [21], others did not find significant differences with regard to healthy individuals [22,28,29]. In the present study, we found lower absolute and relative numbers of mDCs in MM patients but not in MGUS patients, together with greater numbers of all subsets of PB DCs in PCL patients.…”

“…Accordingly, while some studies found no alterations in MM DCs from these patients [28,29], others have reported lower expression levels of HLA-DR, CD40, and CD80, together with a lower antigen-presenting capacity and failure to upregulate CD80 expression [21,22]. Some of these discrepancies could be a result, at least to a certain extent, of either the different subpopulations of DCs analyzed after in vitro culture or the distinct technical approaches employed [21,22,28,29].…”

“…At present, the knowledge about DCs from MM patients remains limited, and contradictory results have been reported regarding their phenotypic and functional characteristics [21,22,28,29]. Accordingly, while some studies found no alterations in MM DCs from these patients [28,29], others have reported lower expression levels of HLA-DR, CD40, and CD80, together with a lower antigen-presenting capacity and failure to upregulate CD80 expression [21,22].…”

Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6

“…10,14 Conversely, DCs generated in vitro from monocyte precursors are capable of efficient T-cell stimulation. 17,24,26,27 These studies suggest that circulating PBDCs may not be optimal vehicles for antigen delivery in immunotherapy trials of cancer. The inhibitory effect of IL-6 was abrogated by anti-IL-6 antibodies.…”

Dendritic cells accumulate in the bone marrow of myeloma patients where they protect tumor plasma cells from CD8+ T-cell killing

“…Frequency, phenotype, and function of these cells have been described to be altered by some authors and normal by others. Moreover, different protocols of DC purification and maturation and different ways of measuring DC activity have produced data [20][21][22][23][24][25][26] that cannot be compared and that do not often include MGUS patients.…”