{
  "abstract": "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.",
  "abstract_shown": true,
  "affiliations": [
    "Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Luz María Palacios"
    },
    {
      "affs": [
        0
      ],
      "name": "Nicolás Daniel Dho"
    },
    {
      "affs": [
        0
      ],
      "name": "Cintia Liliana Araujo Furlán"
    },
    {
      "affs": [
        0
      ],
      "name": "Guadalupe López Menichetti"
    },
    {
      "affs": [
        0
      ],
      "name": "Federico Ruiz Moreno"
    },
    {
      "affs": [
        0
      ],
      "name": "Laura Guantay"
    },
    {
      "affs": [
        0
      ],
      "name": "Sofía Daiana Castell"
    },
    {
      "affs": [
        0
      ],
      "name": "María Esperanza Felici"
    },
    {
      "affs": [
        0
      ],
      "name": "Gastón Soria"
    },
    {
      "affs": [
        0
      ],
      "name": "Belkys Maletto"
    },
    {
      "affs": [
        0
      ],
      "name": "María Inés Crespo"
    },
    {
      "affs": [
        0
      ],
      "name": "Gabriel Morón"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dxkq9mwkd9ke5.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1946712",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668838/?tool=EBI",
  "id": "dxkq9mwkd9ke5",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13668838",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|Immunotherapy and Immune Responses"
    ]
  ],
  "openalex": "W7215101485",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668838/pdf/?tool=EBI",
  "pmcid": "PMC13668838",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/dxkq9mwkd9ke5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:18Z",
      "native_id": "PMC:PMC13668838",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13668838"
    },
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1946712",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1946712/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immunotherapy and Immune Responses",
      "subfield": "immunology"
    }
  ],
  "title": "Pimozide enhances antigen cross-presentation and promotes cytotoxic CD8+ T cell immunity by stimulating dendritic cells",
  "title_text": "Pimozide enhances antigen cross-presentation and promotes cytotoxic CD8+ T cell immunity by stimulating dendritic cells",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:15Z",
  "url": "https://research.draconitic.com/paper/dxkq9mwkd9ke5",
  "venue": "Frontiers in immunology",
  "versions": []
}