{
  "abstract": "TREX1 has recently emerged as a promising therapeutic target in cancer owing to its role in degrading cytosolic DNA and suppressing type I interferon signaling. However, the nature of the immunostimulatory DNA species degraded by TREX1 remains elusive. Here, we show that TREX1 deficiency in murine lung and melanoma tumor cells leads to a substantial, MRE11-dependent increase in short cytosolic DNA fragments that originate preferentially from transcriptionally active regions of the genome, without a corresponding increase in micronuclei. These fragments robustly activate interferon-stimulated genes and drive differentiation of pro-inflammatory macrophages. In syngeneic mice, tumors derived from Trex1-knockout cells exhibit delayed growth, increased sensitivity to anti-PD-1 immune checkpoint blockade, and extended survival. These effects depend on an intact immune system and foster durable anti-tumor memory. Together, our results reveal that short, transcription-derived cytosolic DNA fragments are key TREX1 substrates mediating immune activation in cancer, establishing TREX1 inhibition as a compelling strategy to enhance tumor immunogenicity.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "Chun-Yen Yang"
    },
    {
      "name": "Bayan Chami"
    },
    {
      "name": "Chiara Ursino"
    },
    {
      "name": "Silpa Mary Johnson"
    },
    {
      "name": "Julien Faget"
    },
    {
      "name": "Clément Mettling"
    },
    {
      "name": "Laurent Gros"
    },
    {
      "name": "Philippe Pasero"
    },
    {
      "name": "Yea-Lih Lin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/af8e03jb0e0j1.bib",
  "cited_by": 0,
  "doi": "10.1038/s44319-026-00961-8",
  "fulltext_url": null,
  "id": "af8e03jb0e0j1",
  "issns": [
    "1469-221X",
    "1469-3178"
  ],
  "landing_url": "https://hal.science/hal-05804257v1",
  "language": "en",
  "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": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "2403|interferon and immune responses"
    ]
  ],
  "openalex": "W7221999457",
  "pdf_url": "https://hal.science/hal-05804257/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-15",
  "publisher": "EMBO Press",
  "ris": "https://research.draconitic.com/paper/af8e03jb0e0j1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:58Z",
      "native_id": "hal-05804257",
      "source": "hal",
      "url": "https://hal.science/hal-05804257v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|interferon and immune responses",
      "subfield": "immunology"
    }
  ],
  "title": "TREX1 limits anti-tumor immunity by degrading short cytosolic DNA molecules",
  "title_text": "TREX1 limits anti-tumor immunity by degrading short cytosolic DNA molecules",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:58Z",
  "url": "https://research.draconitic.com/paper/af8e03jb0e0j1",
  "venue": "EMBO Reports",
  "versions": []
}