{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:01:04Z","timestamp":1790834464657,"version":"4.1.0"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    The activation of cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    T cells against exogenous antigens\u2014such as those derived from tumors or internalized pathogens\u2014depends 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\n                    <jats:sup>+<\/jats:sup>\n                    T cell activation and proliferation\n                    <jats:italic>in vivo<\/jats:italic>\n                    , enhanced IFN-\u03b3 production by antigen-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    , and augmented cytotoxic T lymphocyte responses\n                    <jats:italic>in vivo<\/jats:italic>\n                    . 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\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    T cell immunity in the context of next-generation cancer immunotherapies.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1946712","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:41:30Z","timestamp":1790833290000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pimozide enhances antigen cross-presentation and promotes cytotoxic CD8+ T cell immunity by stimulating dendritic cells"],"prefix":"10.3389","volume":"17","author":[{"given":"Luz Mar\u00eda","family":"Palacios","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica, Facultad de Ciencias Qu\u00edmicas, Universidad Nacional de C\u00f3rdoba","place":["C\u00f3rdoba, Argentina"]},{"name":"Centro de Investigaciones en Bioqu\u00edmica Cl\u00ednica e 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