{
  "abstract": "Regulatory and dysfunctional CD4+ T cell states contribute to immune evasion in breast cancer (BC), but the molecular programs associated with these phenotypes remain incompletely understood. Here, we identify FLT3 ligand (FLT3LG) as a γ-chain (γc) cytokine-responsive factor enriched in CD4+ T cells of BC. Public transcriptomic and scRNA-seq analyses showed that FLT3LG expression was linked to Treg-enriched immune regulatory signatures. In Jurkat T cells, FLT3LG overexpression (OE) increased regulatory markers and inhibitory receptors while reducing effector cytokine expression and proliferative capacity, consistent with a regulatory-like and reduced effector phenotype rather than bona fide Treg differentiation. In BC co-culture models, HER2+ BC cell lines induced FLT3LG and FOXP3 expression in Jurkat and primary human T cells. FLT3LG-OE T cells were further associated with increased Ki-67 expression and reduced apoptosis in co-cultured BC cells, as well as altered CFSE profiles of primary responder T cells. Mechanistically, γc cytokines induced FLT3LG expression through STAT5-dependent signaling. In a syngeneic mammary tumor model, FLT3LG expression increased in CD4+ T cells during tumor progression, particularly within the Treg subset. Consistently, clinical dataset analyses showed that high FLT3LG expression was associated with poor outcomes in HER2+ and highly proliferative BC contexts. Together, these findings reveal a γc cytokine-STAT5-FLT3LG regulatory circuit linked to CD4+ T cell immunoregulation in BC.\n\nGraphical abstract:\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00262-026-04492-y.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biochemistry, BK21 Plus and The Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Gwanak-ro1, Gwanak-gu, Seoul, 08826 Republic of Korea",
    "Comparative Medicine Disease Research Center, Seoul National University, Seoul, 08826 Republic of Korea",
    "Present Address: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yeo-Jin Im"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Hyeon-Ji Hwang"
    },
    {
      "affs": [
        1
      ],
      "name": "Chae-Yi Kim"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Je-Yoel Cho",
      "orcid": "0000-0003-1030-3577"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ffefs4h3qx385.bib",
  "cited_by": 0,
  "doi": "10.1007/s00262-026-04492-y",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710474/",
  "id": "ffefs4h3qx385",
  "issns": [
    "0340-7004",
    "1432-0851"
  ],
  "landing_url": "https://doi.org/10.1007/s00262-026-04492-y",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2403|T-cell and B-cell Immunology"
    ]
  ],
  "openalex": "W7171548370",
  "pdf_url": null,
  "pmcid": "PMC13710474",
  "pmid": "42934436",
  "published": "2026-07-28",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/ffefs4h3qx385.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:27Z",
      "native_id": "PMC13710474",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s00262-026-04492-y"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|T-cell and B-cell Immunology",
      "subfield": "immunology"
    }
  ],
  "title": "FLT3LG induction by γ-chain cytokine promotes regulatory-like CD4+ T cell features in breast cancer",
  "title_text": "FLT3LG induction by γ-chain cytokine promotes regulatory-like CD4+ T cell features in breast cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:27Z",
  "url": "https://research.draconitic.com/paper/ffefs4h3qx385",
  "venue": "Cancer Immunology, Immunotherapy : CII",
  "versions": []
}