Deficient T _H-1 responses from TNF-a-matured and α-CD40-matured dendritic cells

The ultimate success of dendritic cell (DC) vaccination for the active immunotherapy of neoplasia is thought to be dependent on a very large number of variables, including DC generation protocol, loading methodology, dose, route of administration, and maturation method. Although the use of a maturation cocktail comprising interleukin (IL)-1β, tumor necrosis factor-α, IL-6, and prostaglandin E ₂ (ITIP) has recently appeared in the literature, much of the data in the basic and clinical literature have been generated using DCs matured with the single inflammatory cytokine TNF-α. Here, we demonstrate that DCs matured with TNF-α alone or in combination with CD40 agonism are highly deficient, both physiologically and functionally, in comparison with DCs matured with IL-1β, TNF-α, IL-6, and prostaglandin E ₂. Empirically, the data suggest that DCs matured with these agents are deficient in the induction of type 1 T-helper responses. We further speculate that DCs matured by these methods might be suboptimal for the priming of naive responses.