{
  "abstract": "Background: Immune checkpoint blockade has expanded the therapeutic landscape of bladder cancer, yet durable clinical benefit remains limited, and the tissue-level ecological determinants of therapeutic resistance are incompletely understood. Intratumoral microbiota are increasingly recognized as spatially organized components of cancer ecosystems, but whether microbial dysbiosis within bladder cancer tissues functionally shapes antitumor immunity remains unclear.\n\nMethods: We integrated contamination-controlled 2bRAD-M microbiome profiling with fluorescence in situ hybridization, single-cell transcriptomics, metabolomics, clinical annotation, organoids, and mouse models to characterize intratumoral microbial states and investigate their roles in immune remodeling and immunotherapy response.\n\nResults: Bladder tumors harbored compositionally heterogeneous intratumoral microbial states. Enrichment of Klebsiella pneumoniae (K. pneumoniae) was associated with aggressive disease and reduced immunotherapy benefit, with receiver operating characteristic AUCs of 0.77 and 0.72 in the discovery and validation cohorts, respectively. Mechanistically, K. pneumoniae-associated valylphenylalanine (Val-Phe engaged an SLC15A1-linked epithelial response, activated NF-κB/p65 signaling, and induced an immunoregulatory cytokine program that promoted M2-like macrophage polarization, impaired CD8+ T-cell effector function, remodeled the tumor immune microenvironment, and limited anti-PD-1 efficacy. SLC15A1-guided virtual screening identified MK-0557 as a candidate modulator that restrained tumor growth and improved anti-PD-1 response in preclinical models.\n\nConclusions: These findings identify intratumoral microbial dysbiosis as a functional regulator of metabolic-immune remodeling in bladder cancer and define the K. pneumoniae-associated valylphenylalanine–SLC15A1–NF-κB/p65 axis as a potential therapeutic target for overcoming resistance to immune checkpoint blockade.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China",
    "State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China",
    "Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China",
    "Department of Urology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China",
    "Department of Radiation Oncology, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, China",
    "Guangdong Microbial Culture Collection Center, Guangzhou, China",
    "Key Laboratory of Agricultural Microbiomics and Precision Application (MARA), Guangzhou, China",
    "Key Laboratory of Agricultural Microbiome (MARA), Guangzhou, China",
    "State Key Laboratory of Applied Microbiology Southern China, Guangzhou, China",
    "Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Ruilin Zhuang",
      "orcid": "0009-0005-0533-2623"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Zhiming Wu"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Runhao Zheng"
    },
    {
      "affs": [
        3
      ],
      "name": "Yuelong Chen"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Xingliang Tan",
      "orcid": "0000-0002-4015-4982"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Xinpei Deng",
      "orcid": "0000-0001-9973-2559"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Chichen Zhang"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Jiamin Zeng"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Yanjun Wang"
    },
    {
      "affs": [
        4
      ],
      "name": "Haixia He"
    },
    {
      "affs": [
        5,
        6,
        7,
        8,
        9
      ],
      "name": "Yang Liu"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Qianghua Zhou"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Kai Yao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4qngwsnx6b9d2.bib",
  "cited_by": 0,
  "doi": "10.1136/jitc-2026-016574",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13723928/",
  "id": "4qngwsnx6b9d2",
  "issns": [
    "2051-1426"
  ],
  "landing_url": "https://doi.org/10.1136/jitc-2026-016574",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "1506"
    ],
    [
      "heading",
      "Basic and Translational Cancer Immunology"
    ],
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7224020578",
  "pdf_url": null,
  "pmcid": "PMC13723928",
  "pmid": "42946394",
  "published": "2026-10-27",
  "publisher": "BMJ Publishing Group",
  "ris": "https://research.draconitic.com/paper/4qngwsnx6b9d2.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:22:28Z",
      "native_id": "PMC13723928",
      "source": "pmc",
      "url": "https://doi.org/10.1136/jitc-2026-016574"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "Intratumoral Klebsiella pneumoniae drives metabolic-immune remodeling and immunotherapy resistance in bladder cancer",
  "title_text": "Intratumoral Klebsiella pneumoniae drives metabolic-immune remodeling and immunotherapy resistance in bladder cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:20:39Z",
  "url": "https://research.draconitic.com/paper/4qngwsnx6b9d2",
  "venue": "Journal for Immunotherapy of Cancer",
  "versions": []
}