Functional repertoire of dendritic cells generated in granulocyte macrophage-colony stimulating factor and interferon-alpha

Monocyte-derived dendritic cells (DCs) generated in granulocyte macrophage-colony stimulating factor GM-CSF) and interleukin-4 (IL-4–DCs) are used to enhance antitumor immunity in cancer patients, although recent evidence suggests that their functional repertoire may be incomplete; in particular, IL-4–DCs appear unable to induce type 2 cytokine-producing T helper (Th) cells. To assess whether type 1 interferon (IFN) could replace IL-4 and generate DCs with a more complete repertoire, we characterized in detail DCs generated from human monocytes cultured with GM-CSF and IFN-α (IFN–DCs). We found that IFN-α induces DC differentiation more efficiently than IL-4, yielding similar numbers of DCs in a shorter time and that this differentiation persists upon removal of cytokines. Although IFN–DCs had a more mature immunophenotype than IL-4–DCs, showing higher expression of CD80, CD86, and CD83, they still preserved comparable endocytic and phagocytic capacities and responsiveness to maturation stimuli. IFN–DCs had strong antigen-presenting capacity, inducing intense proliferation of T cells to alloantigens or influenza virus. Moreover, IFN–DCs produced lower levels of IL-12p70 and higher levels of IFN-α, IL-4, and IL-10 than IL-4–DCs. As a consequence of this different pattern of cytokine secretion, IFN–DCs induced T cells to produce type 1 (IFN-γ) and type 2 (IL-4 and IL-10) cytokines, and as expected, IL-4–DCs induced only Th1 differentiation. As immune responses with extreme Th1 bias are considered inadequate for the induction of optimal, systemic antitumor immunity, the ability of IFN–DCs to promote more balanced cytokine responses may suggest the advisability to consider these cells in the development of future, DC-based immunotherapy trials.