2026-10-14T05:35:05Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34039365 2026-10-01T05:38:06Z category_696 portal_316 item_type_1 month_year_10_2026

Image 3_Pimozide enhances antigen cross-presentation and promotes cytotoxic CD8+ T cell immunity by stimulating dendritic cells.jpeg Luz María Palacios (25152765) Nicolás Daniel Dho (25152768) Cintia Liliana Araujo Furlán (25152771) Guadalupe López Menichetti (25152774) Federico Ruiz Moreno (17018229) Laura Guantay (15016167) Sofía Daiana Castell (25152777) María Esperanza Felici (25152780) Gastón Soria (306266) Belkys Maletto (19331036) María Inés Crespo (14909826) Gabriel Morón (345200) Genetic Immunology adjuvant cross-presentation/priming cytotoxic T lymphocytes (CTL) dendritic cells pimozide <p>The activation of cytotoxic CD8⁺ T cells requires antigen presentation in the context of major histocompatibility complex class I (MHC-I). 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. Mechanistically, pimozide reshapes antigen-processing pathways in DCs by increasing reactive oxygen species production and altering endosomal physiology, thereby creating a biochemical environment that favors antigen cross-presentation. Moreover, pimozide treatment reduces STAT5 levels in DCs, and pharmacological inhibition of STAT5 with an independent inhibitor recapitulates the enhancement of cross-presentation and CD8⁺ T cell activation, suggesting STAT5 signaling as a mediator of this effect. Together, these findings reveal an unrecognized immunomodulatory activity of pimozide on DCs and establish a conceptual framework for the pharmacological repositioning of small molecules to reprogram DC function. This work ultimately opens new avenues for amplifying cytotoxic CD8⁺ T cell immunity in the context of next-generation cancer immunotherapies.</p> 2026-10-01T05:38:06Z Image Figure 10.3389/fimmu.2026.1946712.s004 https://figshare.com/articles/figure/Image_3_Pimozide_enhances_antigen_cross-presentation_and_promotes_cytotoxic_CD8_T_cell_immunity_by_stimulating_dendritic_cells_jpeg/34039365 CC BY 4.0