(391b) Cytokine-independent, Physiologic Production of Dendritic Cells via Platelet P-selectin for Immunotherapy

Dendritic cells (DCs) are adept at cross-presentation and initiation of antigen–specific immunity. For therapy, DCs produced by in vitro differentiation of monocytes in the presence of exogenous cytokines have been met with limited clinical success. We hypothesized that DCs produced in a physiological manner maybe more effective and discovered that platelets activate a cross-presentation program in peripheral blood monocytes with rapid (18h) maturation into physiological DCs “phDC”. phDC differentiation was concomitant with formation of an “adhesion synapse” enriched with platelet P-selectin and monocyte PSGL1. Importantly, compared to conventional DCs, phDCs were more effective in murine and human models in induction of tumor-specific T cell immunity. Our findings suggest a cytokine-independent physiologic strategy for DC maturation and a potentially effective alternative for DC-based immunotherapy.