{
  "abstract": "Targeted alpha therapy is generally evaluated by absorbed dose and direct tumor-cell killing, but whether alpha-particle-injured tumor cells can induce systemic antitumor immunity remains poorly defined. We investigated the immunogenic consequences of astatine-211 (211At) injury in a prophylactic melanoma vaccination-challenge model. B16F10 cells were exposed ex vivo to 211At, etoposide, or ultraviolet irradiation under conditions that reduced viable-cell counts at 24 hours to approximately 40% of untreated controls. Injured cells were administered subcutaneously to syngeneic C57BL/6J mice before intravenous challenge with viable B16F10 cells. Vaccination with cells exposed to 1 MBq/mL 211At suppressed pulmonary metastasis, reduced regulatory T-cell proportions, and elicited tumor-reactive interferon-{gamma} responses and antibodies. Transcriptomic profiling revealed enrichment of type I interferon, inflammatory, and chemokine-related signatures, together with suppression of cell-cycle, translation, and metabolic programs. At the cellular level, 211At injury was accompanied by {gamma}H2AX accumulation, G2/M arrest, increased reactive oxygen species and cytosolic double-stranded DNA, and senescence-like changes. These features arose without consistent increases in classical damage-associated molecular patterns or prominent induction of senescence-associated secretory phenotype factors at 1 MBq/mL. In vivo pharmacologic inhibition of stimulator of interferon genes (STING) signaling attenuated the antimetastatic effect of vaccination. Together, these findings demonstrate that 211At injury can generate an immunostimulatory tumor-cell state characterized by DNA damage and altered inflammatory signaling. STING contributes to the resulting immune protection, highlighting immunogenic tumor-cell conversion as a consideration in the design of targeted alpha therapies.",
  "abstract_shown": true,
  "affiliations": [
    "The University of Osaka"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "K. Mayusumi"
    },
    {
      "name": "S. Magara"
    },
    {
      "name": "X. Huang"
    },
    {
      "name": "K. Kaneda-Nakashima"
    },
    {
      "name": "K. Ooe"
    },
    {
      "name": "M. Murakami"
    },
    {
      "name": "A. Toyoshima"
    },
    {
      "name": "H. Haba"
    },
    {
      "name": "X. Yin"
    },
    {
      "name": "K. Fukase"
    },
    {
      "name": "A. Shimoyama"
    },
    {
      "affs": [
        0
      ],
      "name": "K. Kabayama"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c2xac78x1a6f5.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.22.760895",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.760895v1.full",
  "id": "c2xac78x1a6f5",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.760895v1",
  "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",
      "immunology"
    ],
    [
      "openalex",
      "2403|Immunotherapy and Immune Responses"
    ]
  ],
  "openalex": "W7223943913",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.760895v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/c2xac78x1a6f5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:53Z",
      "native_id": "10.64898/2026.10.22.760895",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.22.760895v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Astatine-211 injury induces an immunostimulatory melanoma-cell state and promotes systemic antitumor immunity",
  "title_text": "Astatine-211 injury induces an immunostimulatory melanoma-cell state and promotes systemic antitumor immunity",
  "type": "preprint",
  "updated_at": "2026-10-30T12:29:53Z",
  "url": "https://research.draconitic.com/paper/c2xac78x1a6f5",
  "venue": "bioRxiv",
  "versions": []
}