{
  "abstract": "Intravesical Bacillus Calmette–Guérin (BCG) remains the standard adjuvant treatment for high-risk non-muscle-invasive bladder cancer (NMIBC), yet the mechanisms underlying its durable clinical benefit and treatment resistance remain incompletely understood. Although BCG has traditionally been regarded as a local immunotherapy, emerging clinical and preclinical evidence suggests that intravesical BCG can induce trained-immunity-associated systemic immune changes, including alterations in circulating innate immune responses and hematopoietic programming. In this Review, we propose the bone marrow–bladder axis as a hypothesis-generating conceptual framework linking local microbial sensing with systemic hematopoietic responses that may contribute to sustained myeloid and adaptive antitumor immunity. Building upon this framework, we further introduce the Failure-to-Train (FTT) model, which proposes that selected immune-training-related mechanisms may contribute to heterogeneous patterns of BCG failure through disruption of productive immune training at distinct stages of the proposed immune-training circuit. Finally, we discuss the implications of this framework for biomarker development, experimental validation and mechanism-guided immunotherapy. By considering systemic immune training as a potential contributor to BCG responses, this Review provides a conceptual framework for investigating treatment response and resistance and for developing testable strategies for next-generation immunotherapy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Geriatric, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine",
    "Department of Colorectal and Anal Surgery, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine",
    "Department of Urology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine",
    "Department of General Practice, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine",
    "Department of Emergency, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine"
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Meng Yang"
    },
    {
      "affs": [
        1
      ],
      "name": "Yu Guo"
    },
    {
      "affs": [
        2
      ],
      "name": "Yu-zhao Shen"
    },
    {
      "affs": [
        3
      ],
      "name": "Yan-Li Sun"
    },
    {
      "affs": [
        4
      ],
      "name": "Dai-Ju Ma"
    },
    {
      "affs": [
        2
      ],
      "name": "Yuan-Jia Tang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ehtv4f2jerr7f.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1945559",
  "fulltext_url": "https://europepmc.org/articles/PMC13681358",
  "id": "ehtv4f2jerr7f",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1945559/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|Immune responses and vaccinations"
    ]
  ],
  "openalex": "W7220704530",
  "pdf_url": "https://europepmc.org/articles/PMC13681358?pdf=render",
  "pmcid": "PMC13681358",
  "pmid": "42903705",
  "published": "2026-10-06",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/ehtv4f2jerr7f.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1945559",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1945559/full"
    },
    {
      "first_seen": "2026-10-30T12:19:57Z",
      "native_id": "MED:42903705",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42903705"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immune responses and vaccinations",
      "subfield": "immunology"
    }
  ],
  "title": "Reprogramming innate immune memory in bladder cancer: the proposed bone marrow–bladder axis and next-generation BCG-based immunotherapies",
  "title_text": "Reprogramming innate immune memory in bladder cancer: the proposed bone marrow–bladder axis and next-generation BCG-based immunotherapies",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:57Z",
  "url": "https://research.draconitic.com/paper/ehtv4f2jerr7f",
  "venue": "Frontiers in Immunology",
  "versions": []
}