Immunostimulatory properties of human dendritic cells generated using IFN-beta associated either with IL-3 or GM-CSF

Despite limited clinical efficacy in large trials, dendritic cells (DC)-based immunization has yielded impressive responses in some patients. Key questions remain to be solved in order to optimize this therapeutic vaccine. Among them, the nature of the DC type used and its state of maturation are pivotal. Besides myeloid DC which are mostly used in clinical trials, a new DC type has been recently described resulting from the differentiation of monocytes in the presence of type I IFNs. In the present study, we analyze the features of type I IFNs DC generated in the presence of either IL-3 (IL-3-DC) or GM-CSF (GM-CSF-DC) and compare their capacity to respond to poly(I:C) and to subsequently trigger T-cell activation. The two DC types disclose a similar immunophenotype characterized by high levels of chemokines receptors, co-stimulatory and HLA molecules expression. After poly(I:C) maturation, both DC types display a marked upregulation of CD80, CD83 and CD86 and the same pattern of gene expression. In addition, poly(I:C) stimulated them to secrete IFN-alpha and IL-12p70. Both DC types elicit potent allogeneic reactions. Priming of autologous T cells by IL-3-DC or GM-CSF-DC pulsed with an HLA-A2 restricted melan-A derived peptide, lead to the expansion of peptide specific CTL secreting high amounts of IFN-gamma. We conclude that poly(I:C) matured IL-3-DC and GM-CSF-DC share similar phenotype and functional properties including the capacity to prime tumor-associated antigen specific CTL.