Journal of immunotherapy
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Journal of immunotherapy · Sep 2012
Induction of antitumor immunity ex vivo using dendritic cells transduced with fowl pox vector expressing MUC1, CEA, and a triad of costimulatory molecules (rF-PANVAC).
The fowl pox vector expressing the tumor-associated antigens, mucin-1 and carcinoembryonic antigen in the context of costimulatory molecules (rF-PANVAC) has shown promise as a tumor vaccine. However, vaccine-mediated expansion of suppressor T-cell populations may blunt clinical efficacy. We characterized the cellular immune response induced by ex vivo dendritic cells (DCs) transduced with (rF)-PANVAC. ⋯ Moreover, Tregs expressed high levels of Th2 cytokines [interleukin (IL)-10, IL-4, IL-5, and IL-13] together with phosphorylated STAT3 and STAT6. In contrast, the vaccine-expanded Treg population expressed high levels of Th1 cytokines IL-2 and interferon-γ and the proinflammatory receptor-related orphan receptor γt (RORγt) and IL-17A suggesting that these cells may share effector functions with conventional TH17 T cells. These data suggest that Tregs expanded by rF-PANVAC-DCs, exhibit immunosuppressive properties potentially mediated by Th2 cytokines, but simultaneous expression of Th1 and Th17-associated factors suggests a high degree of plasticity.