Abstract 3828: Uncarinic acid C plus IFN-γ generates monocyte-derived dendritic cells and induces a potent Th1 polarization with capacity to migrate

Abstract

Abstract Uncarinic acid C (URC) is triterpene isolated from Uncaria rhynchophylla and modulates human DC function in a fashion that favors Th1 cell polarization depending on TLR4 signaling. The induction of dendritic cells (DC) is critical for the induction of Ag-specific T lymphocyte responses and may be essential for the development of human vaccines relying on T cell immunity. Monocyte-derived DCs are used as adjuvant cells in cancer immunotherapy and have shown promising results. We studied the effect of interferons (IFN-α and IFN-γ) and TNF-α on phenotypic and functional maturation, and cytokine production of URC-primed DC in vitro. Human monocytes were exposed to URC alone, or in combination with TNF-α, IFN-α and IFN-γ. All three cytokines induced phenotypically mature DC. The expression levels of CD38 and CCR7 on URC-primed DC were enhanced by IFN-γ and IFN-γ augmented the T cell stimulatory capacity in allo MLR to URC-primed DC. DC matured with URC plus IFN-γ produce high levels of IL-12p70 upon CD40 triggering. IFN-γ secretion from naïve T cells co-cultured with URC-primed DC also augmented by IFN-γ. In addition, DC maturated with URC plus IFN-γ has an intermediate migratory capacity towards CCL19 and CCL21. In contrast, surface molecule up-regulation and function of URC-primed DC were slightly enhanced by TNF-α and IFN-α. These data support that DC differentiated with URC in combination with IFN-γ might be used on DC-based vaccine for cancer immunotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3828.