{
  "abstract": "Immune checkpoint inhibitors benefit only a subset of patients with urothelial carcinoma, and bulk biomarkers may not capture spatially organized stromal and vascular programs that restrict immune access. We performed a retrospective public multi-cohort transcriptomic study to examine whether a cancer-associated fibroblast (CAF)/TGF-beta/endothelial barrier direction is associated with immune exclusion and checkpoint resistance in bladder cancer. GSE171351 was used for spatial discovery, GSE319536 for external spatial recurrence testing, TCGA-BLCA for prognosis-oriented support, and IMvigor210, GSE176307 and GSE328930/DUTRENEO for treatment-response projection. In the four-section discovery cohort, rank-5 non-negative matrix factorization separated an E2 barrier-enriched program from an E4 hypoxic epithelial program, although component assignment was strongly associated with section identity. The external cohort reproduced the direct CAF/TGF-beta/endothelial barrier direction in 22 of 22 sections but did not reproduce E2/E4 mutual exclusivity: projected E2 and E4 were positively correlated (rho = 0.928). In IMvigor210, top-quartile E2-high tumors showed suggestive, but not statistically conclusive, evidence of anti-PD-L1 non-response after full biologic covariate adjustment (OR=2.57, 95% CI 1.00–6.64, p = 0.051; delta AUC = 0.009). A prespecified heuristic barrier-exclusion score was associated with non-response in exploratory fixed- and random-effects summaries (OR=1.52, 95% CI 1.20–1.92), including a sensitivity analysis excluding GSE328930. These results identify a recurrent barrier direction rather than a universal two-niche architecture and support a hypothesis-generating mechanism-to-translation framework that requires prospective spatial and pathology-level validation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Urology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yuye Wu"
    },
    {
      "name": "Guangjie Li"
    },
    {
      "name": "Lixing Jiang"
    },
    {
      "name": "Chaohong Zhang"
    },
    {
      "name": "Huilong Fang"
    },
    {
      "name": "Haiqing Fan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/at23b6q2vwqbq.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0358043",
  "fulltext_url": null,
  "id": "at23b6q2vwqbq",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0358043",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Biomarkers"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Hypoxia"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune response"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune response"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancer treatment"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms/Genitourinary tract tumors/Bladder cancer"
    ],
    [
      "plos",
      "/Medicine and health sciences/Oncology/Cancers and neoplasms/Malignant tumors"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pulmonology/Medical hypoxia"
    ],
    [
      "plos",
      "/Medicine and health sciences/Urology/Genitourinary cancers/Bladder cancer"
    ]
  ],
  "openalex": "W7214025853",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0358043&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-22",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/at23b6q2vwqbq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:43Z",
      "native_id": "10.1371/journal.pone.0358043",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0358043"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:immunology",
      "subfield": "immunology"
    },
    {
      "field": "medicine",
      "origin": "plos:oncology",
      "subfield": "oncology"
    }
  ],
  "title": "A recurrent cancer-associated fibroblast/TGF-beta/endothelial barrier direction is associated with immune exclusion and checkpoint resistance in bladder cancer: a public multi-cohort transcriptomic study",
  "title_text": "A recurrent cancer-associated fibroblast/TGF-beta/endothelial barrier direction is associated with immune exclusion and checkpoint resistance in bladder cancer: a public multi-cohort transcriptomic study",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:43Z",
  "url": "https://research.draconitic.com/paper/at23b6q2vwqbq",
  "venue": "PLOS One",
  "versions": []
}