{
  "abstract": "FLASH radiotherapy delivers radiation at ultra-high dose rates and has been demonstrated to spare normal tissue compared to standard radiotherapy, but it is not known if dose rate also modifies tumor response. Here we compare a single 13.5 Gy fraction of proton irradiation delivered at FLASH (F-PRT) or Standard (S-PRT) dose rate in immunocompetent C57BL/6 mice bearing EO771 or AT3 triple-negative mammary tumors. At this identical physical dose, F-PRT delays tumor growth more than S-PRT at both heterotopic and orthotopic sites. The effect is largest in EO771, where F-PRT also prolongs tumor-volume endpoint-free survival and reduces the emergence of lung metastases relative to S-PRT. F-PRT induces earlier intratumoral STING expression and IRF3 nuclear translocation, higher type I interferon levels and greater CD8+ T-cell infiltration. CD8+ T-cell depletion or systemic STING inhibition abolishes the F-PRT advantage. Combined with anti-PD-1 and agonistic anti-CD40, both modalities produce durable complete responses that reject contralateral rechallenge, but F-PRT limits tumor progression before response and accelerates regression. FLASH proton radiotherapy not only improves normal-tissue tolerance, but also antitumor immunity, suggesting that ultra-high dose rate could widen the therapeutic window from both sides.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "name": "P. Loap"
    },
    {
      "name": "I. Paraskevaidis"
    },
    {
      "name": "C. Cheptea"
    },
    {
      "name": "K. Kolker"
    },
    {
      "name": "M. Kim"
    },
    {
      "name": "J. Setianegara"
    },
    {
      "name": "K. Singh"
    },
    {
      "name": "I. M. Berianu"
    },
    {
      "name": "J. Metz"
    },
    {
      "name": "R. A. Greenberg"
    },
    {
      "name": "W. B. Bilker"
    },
    {
      "name": "E. Berlin"
    },
    {
      "name": "C. Koumenis"
    },
    {
      "name": "C.-A. Assenmacher"
    },
    {
      "name": "E. Diffenderfer"
    },
    {
      "name": "N. K. Taunk"
    },
    {
      "affs": [
        0
      ],
      "name": "I. I. Verginadis"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b85hm2j9gvkn8.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.19.751623",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.19.751623v1.full",
  "id": "b85hm2j9gvkn8",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.19.751623v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2740|Radiation Therapy and Dosimetry"
    ]
  ],
  "openalex": "W7214003514",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.19.751623v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/b85hm2j9gvkn8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:46Z",
      "native_id": "10.64898/2026.09.19.751623",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.19.751623v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Proton FLASH radiotherapy enhances control of triple-negative breast cancer through STING-IRF3 and CD8+ T-cell immunity",
  "title_text": "Proton FLASH radiotherapy enhances control of triple-negative breast cancer through STING-IRF3 and CD8+ T-cell immunity",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:46Z",
  "url": "https://research.draconitic.com/paper/b85hm2j9gvkn8",
  "venue": "bioRxiv",
  "versions": []
}