Figures & data
Figure 1. IL-12p70-producing dendritic cell (DC)-based vaccines elicit Tc1 immunity leading to clinical responses in melanoma patients. (A and B) Autologous monocyte-derived dendritic cells (DCs) were activated with CD40 ligand (CD40L) and interferon γ (IFNγ), resulting in the generation of functionally mature IL-12p70-producing DCs for administration to cancer patients. The amounts of IL-12p70 secreted by these cells varied dramatically among patients, and we chose to discriminate between high (> 1 ng/106cells/24h) (A) and low (< 1 ng/106cells/24hrs) (B) producers. The DCs producing low levels of IL-12p70 exhibited impaired IL12p35 transcription, resulting in the preferential secretion of IL-12p40 instead of IL-12p70. The levels of IL-12p70 secreted by DCs did not correlate with the magnitude of vaccine-induced gp100-specific CD8+ T-cell responses. However, patients immunized with DCs secreting high IL-12p70 levels developed a Tc1-biased immune response characterized by robust production of IFNγ over IL-5 and IL-13. In contrast, the administration of DCs producing low amounts of IL-12p70 drove the development of Tc2-skewed responses. A correlation was observed between the amounts of IL-12p70 produced by DCs, the development of Tc1 immunity and clinical responses.
