{
  "abstract": "Immune checkpoint inhibitors (ICIs) have transformed the treatment of lung cancer, but checkpoint inhibitor pneumonitis (CIP) remains a potentially life-threatening immune-related adverse event. A subset of patients fails to improve despite adequate glucocorticoid therapy and develops corticosteroid-refractory CIP, which is associated with respiratory failure, substantial mortality, and considerable therapeutic uncertainty. This review critically examines the clinical definition, phenotypic characteristics, immunological mechanisms, and therapeutic evidence for corticosteroid-refractory CIP. Emerging data suggest that refractoriness should not be regarded as a uniform failure of glucocorticoid treatment, but rather as a biologically heterogeneous and dynamically evolving syndrome involving persistent tissue-resident T-cell activation, inflammatory T-cell–myeloid crosstalk, cytokine-network redundancy, innate immune dysregulation, and, in some patients, transition toward maladaptive tissue repair and structural lung remodeling. Current second-line treatments, including mycophenolate mofetil, infliximab, intravenous immunoglobulin, tocilizumab, cyclophosphamide, and calcineurin inhibitors, are supported predominantly by retrospective studies and case-report and case-series evidence, with no established optimal treatment sequence. We therefore propose a hypothesis-generating phenotype-to-therapy framework that distinguishes lymphocyte-dominant, cytokine-dominant, fulminant acute lung injury/diffuse alveolar damage, innate/myeloid-dominant, and organizing/fibrotic-remodeling phenotypes while recognizing their potential overlap and temporal evolution. Translating this framework into clinical practice will require harmonized definitions, longitudinal multimodal phenotyping, treatment-predictive biomarkers, and prospective comparative studies. Ultimately, management should move beyond empirical escalation of immunosuppression toward identifying the dominant biological process at a given disease stage and matching treatment intensity and mechanism accordingly.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Respiratory and Critical Care Medicine, West China Tianfu Hospital, Sichuan University",
    "Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Rong Zhang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xiaoxue Zhang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xiulan He"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Min Xiang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5chthh5j3bwvq.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1983756",
  "fulltext_url": null,
  "id": "5chthh5j3bwvq",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1983756/full",
  "language": null,
  "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",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7224123630",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/5chthh5j3bwvq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1983756",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1983756/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "Corticosteroid-refractory checkpoint inhibitor pneumonitis in lung cancer: biological heterogeneity and mechanism-informed management",
  "title_text": "Corticosteroid-refractory checkpoint inhibitor pneumonitis in lung cancer: biological heterogeneity and mechanism-informed management",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:17Z",
  "url": "https://research.draconitic.com/paper/5chthh5j3bwvq",
  "venue": "Frontiers in Immunology",
  "versions": []
}