{
  "abstract": "Regulatory T cell (Treg) accumulation within the tumor microenvironment is a major contributor to immune evasion and immunotherapy resistance. However, the metabolic signals orchestrating Treg lineage commitment remain poorly defined. We identify that the oxysterol 7α,25-dihydroxycholesterol (7α,25-OHC), produced by Vimentin⁺ stromal cells, acts through GPR183 to promote Treg differentiation and suppressive identity. In patients with gastric cancer (GC), GPR183⁺ Treg infiltration correlates with advanced disease and poor survival. In syngeneic tumor models, conditional GPR183 deletion, specifically in CD4⁺ T cells or Treg cells, demonstrates its cell-intrinsic requirement for high-cholesterol-diet-induced Treg expansion and tumor growth, thereby abrogating immune evasion and restoring CD8⁺ T cell effector function. Mechanistically, 7α,25-OHC-GPR183 signaling activates the AXL-JAK2-STAT5 pathway to reinforce Foxp3 expression. Last, GPR183 antagonism modestly enhances anti-PD-1 efficacy in a model-dependent manner and prevents therapy-induced Treg expansion. These findings identify the 7α,25-OHC-GPR183-AXL axis as a potential metabolic checkpoint linking cholesterol metabolism to immune suppression, suggesting a potential therapeutic strategy to enhance antitumor immunity.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Gastrointestinal Cancer Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.",
    "Tianjin Key Laboratory of Digestive Cancer, Tianjin Clinical Research Center for Cancer, Tianjin, China.",
    "National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.",
    "Department of Gynecologic Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.",
    "Department of Radiation Oncology, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Yang Qu",
      "orcid": "0000-0001-5059-3412"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Yihan Xu",
      "orcid": "0009-0006-2407-3863"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Jingchao Bai",
      "orcid": "0009-0002-5418-5461"
    },
    {
      "affs": [
        0,
        1,
        2,
        4
      ],
      "name": "Yuhan Zhang",
      "orcid": "0000-0002-8511-4562"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Ning Ji",
      "orcid": "0000-0002-5002-6220"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Xinxin Li",
      "orcid": "0009-0006-7792-334X"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Hui Li",
      "orcid": "0000-0002-3526-6664"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/975v48mhxx9w8.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aeh9736",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13721965/?tool=EBI",
  "id": "975v48mhxx9w8",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://www.science.org/doi/abs/10.1126/sciadv.aeh9736",
  "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": [
    [
      "heading",
      "Biomedicine and Life Sciences"
    ],
    [
      "heading",
      "Cancer"
    ],
    [
      "heading",
      "Immunology"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "heading",
      "SciAdv r-articles"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13721965/pdf/?tool=EBI",
  "pmcid": "PMC13721965",
  "pmid": "42962000",
  "published": "2026-10-30",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/975v48mhxx9w8.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:30Z",
      "native_id": "10.1126/sciadv.aeh9736",
      "source": "feed-science",
      "url": "https://www.science.org/doi/abs/10.1126/sciadv.aeh9736"
    },
    {
      "first_seen": "2026-10-31T00:20:32Z",
      "native_id": "10.1126/sciadv.aeh9736",
      "source": "crossref",
      "url": "https://www.science.org/doi/10.1126/sciadv.aeh9736"
    },
    {
      "first_seen": "2026-10-31T12:21:37Z",
      "native_id": "PMC:PMC13721965",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13721965"
    },
    {
      "first_seen": "2026-11-02T03:21:21Z",
      "native_id": "MED:42962000",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42962000"
    },
    {
      "first_seen": "2026-11-03T12:22:33Z",
      "native_id": "PMC13721965",
      "source": "pmc",
      "url": "https://doi.org/10.1126/sciadv.aeh9736"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Immunology",
      "subfield": "immunology"
    },
    {
      "field": "medicine",
      "origin": "heading:Cancer",
      "subfield": "oncology"
    }
  ],
  "title": "GPR183 senses 7α,25-OHC to drive Treg differentiation and tumor immune evasion via AXL-JAK2-STAT5 signaling",
  "title_text": "GPR183 senses 7α,25-OHC to drive Treg differentiation and tumor immune evasion via AXL-JAK2-STAT5 signaling",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:22:33Z",
  "url": "https://research.draconitic.com/paper/975v48mhxx9w8",
  "venue": "Science Advances",
  "versions": []
}