{
  "abstract": "Purpose: A minority of patients with bladder cancer derive lasting benefit from immunotherapy, and current biomarkers capture only part of the biology. We evaluated whether tumor-cell MHC class II defines an immune state associated with outcome across disease stages and after PD-1/PD-L1 blockade. Experimental Design: We localized differential MHC-II activity to malignant epithelial cells by single-nucleus and single-cell RNA sequencing and confirmed HLA-DR expression by immunohistochemistry in 122 specimens. Chromatin profiling and IFN-{gamma} stimulation of cell lines and primary tumors supported derivation of an 11-gene tumor-cell program. Associations were tested in 434 patients with non-muscle-invasive disease, 82 receiving neoadjuvant pembrolizumab, and 288 receiving atezolizumab for metastatic disease. Results: Tumor-cell MHC-II was present in approximately one third of bladder cancers, and malignant cells accounted for the differential signal between MHC-II-high and MHC-II-low tumors. The program was inducible by IFN-{gamma} through JAK/STAT signaling. Within luminal non-muscle-invasive disease, MHC-II-low status was associated with progression (HR 3.31, 95% CI 1.37 to 7.99). In PURE-01, the 11-gene program was associated with pathological complete response (52% versus 24%, p = 0.018) and recurrence-free survival (p = 0.0054), retaining an independent association in models including tumor mutational burden and PD-L1. In bladder-primary metastatic disease, program-high status was associated with overall survival in unadjusted analysis (HR 0.62, 95% CI 0.44 to 0.89); the association did not extend to upper tract tumors (interaction p = 0.0018). Conclusions: Tumor-cell MHC-II defines an inducible state associated with outcomes across bladder cancer stages and after checkpoint blockade, supporting prospective evaluation by RNA and immunohistochemistry.",
  "abstract_shown": true,
  "affiliations": [
    "Dana-Farber Cancer Institute"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 23,
  "authors": [
    {
      "name": "J. Bellmunt"
    },
    {
      "name": "Y. Xie"
    },
    {
      "name": "M. Gomez Munoz"
    },
    {
      "name": "S. Kukreja"
    },
    {
      "name": "S. Walker"
    },
    {
      "name": "R. He"
    },
    {
      "name": "R. Li"
    },
    {
      "name": "X. Qiu"
    },
    {
      "name": "T. Zhang"
    },
    {
      "name": "P. Rodriguez"
    },
    {
      "name": "D. Garcia Gonzalez"
    },
    {
      "name": "I. Epstein"
    },
    {
      "name": "J. Parera"
    },
    {
      "name": "N. Juanpere"
    },
    {
      "name": "M. Lorenzo"
    },
    {
      "name": "O. Buisan"
    },
    {
      "name": "J. Senserrich"
    },
    {
      "name": "P. Servian"
    },
    {
      "name": "T. Silva"
    },
    {
      "name": "M. Brown"
    },
    {
      "name": "C. Cabrera"
    },
    {
      "name": "P. Cejas"
    },
    {
      "affs": [
        0
      ],
      "name": "H. W. Long"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8zqes9vda04cq.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.21.753036",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753036v1.full",
  "id": "8zqes9vda04cq",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753036v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7214359713",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753036v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-21",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/8zqes9vda04cq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:47Z",
      "native_id": "10.64898/2026.09.21.753036",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753036v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "A tumor-cell MHC-II program is associated with checkpoint-blockade outcomes across stages of bladder cancer",
  "title_text": "A tumor-cell MHC-II program is associated with checkpoint-blockade outcomes across stages of bladder cancer",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:47Z",
  "url": "https://research.draconitic.com/paper/8zqes9vda04cq",
  "venue": "bioRxiv",
  "versions": []
}