{
  "abstract": "Immune checkpoint inhibitors (ICIs) provide durable tumor control in some patients, but resistance can develop through tumor-intrinsic and microenvironmental mechanisms. This narrative review examines the metabolic and immune conditions under which ferroptosis may enhance ICI responsiveness or resensitize selected ICI-refractory tumors. Radiotherapy (RT) increases oxidizable phospholipids and can repress SLC7A11, the light-chain component of system xc ⁻ . ICI-activated CD8 ⁺ T cells provide convergent interferon-γ signaling. Tumors can resist this pressure through GPX4, FSP1-CoQ10, mitochondrial DHODH, NRF2-dependent programs, and iron-export pathways. Recent preclinical studies have tested RT with ferroptosis-directed interventions and ICIs. These studies include functional evidence of ferroptosis dependence in radioresistant lung cancer and resensitization of LKB1-deficient, primarily ICI-refractory tumors. The findings support a preclinical rationale for combination therapy, although their causal strength varies. Reversal of clinically defined acquired ICI resistance remains unestablished, and the clinical RT-ICI studies reviewed here did not measure ferroptosis in patients. The immune effects also vary by cell type. Tumor-cell ferroptosis may support immunity, whereas lipid peroxidation in CD8 ⁺ T cells, dendritic cells, or polymorphonuclear myeloid-derived suppressor cells can impair antitumor responses. Translation will require functional validation, cell-resolved biomarkers, achievable drug exposures, and evaluation of RT dose, fractionation, and sequence alongside normal-tissue and immune-cell safety.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Tumor Biological Therapy, Affiliated Cancer Hospital of Inner Mongolia Medical University , ,"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zhenghao Cao"
    },
    {
      "affs": [
        0
      ],
      "name": "Xudong Ao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2d094zyvmk1pn.bib",
  "cited_by": 0,
  "doi": "10.3389/fonc.2026.1954104",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688023/?tool=EBI",
  "id": "2d094zyvmk1pn",
  "issns": [
    "2234-943X"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13688023",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2740|Ferroptosis and cancer prognosis"
    ]
  ],
  "openalex": "W7220918164",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688023/pdf/?tool=EBI",
  "pmcid": "PMC13688023",
  "pmid": null,
  "published": "2026-10-08",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/2d094zyvmk1pn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:59Z",
      "native_id": "PMC:PMC13688023",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13688023"
    },
    {
      "first_seen": "2026-10-30T12:20:13Z",
      "native_id": "10.3389/fonc.2026.1954104",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1954104/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:2234-943X",
      "subfield": "oncology"
    }
  ],
  "title": "Ferroptosis-driven radio-immunosensitization: an emerging mechanistic framework for enhancing response to immune checkpoint inhibitor therapy",
  "title_text": "Ferroptosis-driven radio-immunosensitization: an emerging mechanistic framework for enhancing response to immune checkpoint inhibitor therapy",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:13Z",
  "url": "https://research.draconitic.com/paper/2d094zyvmk1pn",
  "venue": "Frontiers in oncology",
  "versions": []
}