Immune response induced in vitro by CD16(-) and CD16(+) monocyte-derived dendritic cells in patients with metastatic renal cell carcinoma treated with dendritic cell vaccines

Monocyte-derived dendritic cells (mDC) are increasingly used as cancer vaccines. However, human monocytes are a heterogeneous cell population. We showed previously that DC derived from a monocyte subset expressing CD16 (16+mDC) stimulated allogeneic naive T lymphocytes to secrete higher levels of IL-4 than DC derived from regular CD14(high)CD16(-) monocytes (16-mDC). Th1-type responses have been associated with effective antitumor responses, thus the use of mDC containing 16+mDC as cancer vaccines might be disadvantageous. Here, we evaluate the primary and memory immune response elicited in vitro by 16+mDC and 16-mDC in five patients with metastatic renal cell carcinoma vaccinated with autologous mDC pulsed with tumor lysates (TuLy) and keyhole limpet hemocyanin (KLH). After therapy, three of the five patients had stable disease. Surprisingly, patients with longer survival showed the highest amount of peripheral blood CD16+ monocytes. Analysis of KLH-specific antibodies revealed high titers of IgG2 in patients with longer survival. CD4+ T lymphocyte proliferation against KLH and TuLy increased after treatment, and some patients showed an augmented rate of CD4+ T lymphocyte proliferation against KLH (3/5) and TuLy (2/3) when 16+mDC were used as antigen presenting cells (APC). Before treatment, the IFN-gamma/IL-4 ratio against TuLy and KLH was higher when using 16-mDC as APC, but after vaccination four of five patients had an increased ratio for TuLy with 16+mDC. These results suggest that the immune response elicited by 16-mDC and 16+mDC is modified when memory or naive T cells are stimulated, and 16+mDC could favor a stronger and more beneficial antitumoral Th1 memory response in vivo.