Image 2_Pimozide enhances antigen cross-presentation and promotes cytotoxic CD8+ T cell immunity by stimulating dendritic cells.jpeg

While endogenous antigens can directly access this pathway, the priming of CD8⁺ T cells against exogenous antigens—such as those derived from tumors or internalized pathogens—depends on dendritic cell (DC)-mediated antigen cross-presentation. Strategies capable of enhancing DC cross-presentation are therefore of considerable interest for the development of next-generation immunotherapies.

Here, we demonstrate that pimozide, a clinically approved antipsychotic with reported antitumoral and immunomodulatory properties, acts as a pharmacological enhancer of antigen cross-presentation. We show that pimozide-treated DCs display improved cross-presentation of soluble antigens, leading to stronger CD8⁺ T cell activation and proliferation in vivo, enhanced IFN-γ production by antigen-specific CD8⁺ T cells in vitro, and augmented cytotoxic T lymphocyte responses in vivo.