{
  "abstract": "Background: Aberrant glycolysis and lactate accumulation are hallmarks of solid tumors, yet how tumor-derived lactate contributes to tumor progression has not been fully defined. This study intends to examine the role of glycolysis in lung adenocarcinoma (LUAD) growth and immunosuppression, and to explore the underpinning mechanisms.\n\nMethods: Syngeneic Lewis lung carcinoma models and autochthonous KrasLSL-G12D LUAD mice were used. Glycolysis was inhibited by 2-DG or LDH knockdown, followed by tumor growth and immune-cell composition assessments. Therapeutic anti-IL-35 blockade and CD8+ T depletion were performed using neutralizing antibodies. Chitinase 3-like 1 (CHI3L1) expression, regulatory B cell (Breg) polarization, and B-cell-mediated T-cell suppression were assessed by flow cytometry, RNA sequencing, qPCR, ELISA, immunohistochemistry, and co-culture assays. CUT&Tag, chromatin immunoprecipitation, co-immunoprecipitation, and cell-free transferase assays were used to define the lactylation mechanism.\n\nResults: Glycolysis restriction suppressed tumor growth and metastatic colonization, reduced CD1dhiCD5+IL-35+ Bregs, and restored GZMB+CD8+ T cells. CHI3L1 was markedly downregulated after glycolysis inhibition, whereas recombinant CHI3L1 restored IL-13Rα2+ Breg polarization and impaired CD8+ T-cell responses through STAT3 activation. Lactate increased H3K9 lactylation and CHI3L1 expression, while glycolysis inhibition reduced H3K9la enrichment at the Chi3l1 promoter. HBO1 directly catalyzed H3K9 lactylation and promoted CHI3L1 production. Genetic or pharmacological HBO1 blockade reduced Bregs, enhanced cytotoxic T-cell activity, and improved the efficacy of anti-PD-1 therapy.\n\nConclusions: This study demonstrates the participation of an HBO1-H3K9la-CHI3L1–IL-13Rα2-STAT3 axis in tumor glycolysis-established Breg polarization and CD8+ T dysfunction. Targeting HBO1 may provide a strategy to enhance the efficacy of PD-1 blockade in LUAD.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Oncology, Tongji University Affiliated Shanghai Pulmonary Hospital, Shanghai, China",
    "Department of Thoracic Surgery, Tongji University Affiliated Shanghai Pulmonary Hospital, Shanghai, China",
    "Innovation and Incubation Center (IIC), Tongji University Affiliated Shanghai Pulmonary Hospital, Shanghai, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xuyu Gu",
      "orcid": "0009-0004-3232-4293"
    },
    {
      "affs": [
        1
      ],
      "name": "Junjie Zhu"
    },
    {
      "affs": [
        1
      ],
      "name": "Tao Ge"
    },
    {
      "affs": [
        1
      ],
      "name": "Keyi Chen"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Yang Yang"
    },
    {
      "affs": [
        1
      ],
      "name": "Kaiqi Jin"
    },
    {
      "affs": [
        1
      ],
      "name": "Xinnan Xu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f5t48bwsvfw97.bib",
  "cited_by": 0,
  "doi": "10.1136/jitc-2026-015190",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13723905/",
  "id": "f5t48bwsvfw97",
  "issns": [
    "2051-1426"
  ],
  "landing_url": "https://doi.org/10.1136/jitc-2026-015190",
  "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",
      "Clinical Cancer Immunotherapy"
    ],
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7224824783",
  "pdf_url": "https://jitc.bmj.com/content/14/10/e015190.full.pdf",
  "pmcid": "PMC13723905",
  "pmid": "42963104",
  "published": "2026-10-30",
  "publisher": "BMJ Publishing Group",
  "ris": "https://research.draconitic.com/paper/f5t48bwsvfw97.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:22:27Z",
      "native_id": "PMC13723905",
      "source": "pmc",
      "url": "https://doi.org/10.1136/jitc-2026-015190"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "Epigenetic targeting of an HBO1-H3K9la-CHI3L1 axis reduces regulatory B cell-mediated CD8+ T cell dysfunction in lung adenocarcinoma",
  "title_text": "Epigenetic targeting of an HBO1-H3K9la-CHI3L1 axis reduces regulatory B cell-mediated CD8+ T cell dysfunction in lung adenocarcinoma",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:20:38Z",
  "url": "https://research.draconitic.com/paper/f5t48bwsvfw97",
  "venue": "Journal for Immunotherapy of Cancer",
  "versions": []
}