Evaluation of a Dysfunctional and Short-lived Subset of Monocyte-derived Dendritic Cells from Cancer Patients

Monocyte-derived dendritic cells (Mo-DCs) were generated from peripheral blood monocytes of 12 healthy volunteers (hMo-DCs) and 11 patients (pMo-DCs) with malignancies by culture for 7 days with granulocyte- macrophage colony-stimulating factor and interleukin-4. In this study, we focused on the cytogram pattern by FACS analysis. A gate (R1) was set up by which more than 95% of hMo-DCs were contained. Mo-DCs having lower side scatter than the R1 (R2) comprised 4.5% of hMo-DCs and 24.2% of pMo-DCs. Expressions of antigen presentation-related molecules and phagocytic ability in the R2 of pMo-DCs were lower than those in the R1 population. The R2, but not R1, in pMo-DCs decreased in number between days 7 and 14, and expression levels of antigen presentation-related molecules in the living pMo-DCs on day 14 increased. The 11 patients received dendritic cell vaccine therapy with autologous, tumor- pulsed mature Mo-DCs (day 7). The low R2 group (R2≤10%, 3 patients) had a significantly higher positive delayed-type hypersensitivity reaction against autologous tumor-pulsed Mo-DCs than that of the high R2 group (R2>10%, 8 patients) (p<0.001). These results indicate that the R2 of pMo-DCs may be a dysfunctional and short-lived subset. Dendritic cells (DCs), which are known as professional antigen-presenting cells (APCs), can induce both the generation and proliferation of specific cytotoxic T lymphocytes (1-6). DCs capture and process antigens, move to the T-dependent areas of secondary lymphoid organs and stimulate naive T cells. Only DCs are capable of inducing primary sensitization against specific antigens in naive T cells