{
  "abstract": "IntroductionCancer cells can evade interferon (IFN) signaling pressures by suppressing intrinsic innate immune signaling pathways or dedifferentiating, giving rise to immunotherapy-resistant cell states. Therapeutic strategies specifically tailored to account for and eliminate such states remain limited.MethodsHere, we genetically reintroduced stimulator of interferon genes (STING) in dedifferentiated STING-deficient melanoma cells, used AXL receptor tyrosine kinase (AXL) small-molecule inhibition, and analyzed publicly available single-cell RNA-sequencing (scRNA-seq) datasets to examine connections between dedifferentiation and interferon responses in human melanoma.ResultsWe found that STING reintroduction induced type I IFN signaling, increased expression of antigen-presentation genes, and enhanced sensitivity to exogenous type II IFN. STING signaling silenced expression of AXL, a key marker of melanoma dedifferentiation. AXL small-molecule inhibition partially phenocopied STING reintroduction, potentiating antigen-presentation gene expression and enhancing type II IFN sensitivity in dedifferentiated human melanoma cells. Consistently, analysis of publicly available human melanoma scRNA-Seq data revealed tumor cells with concomitant STING loss and AXL gain are positively enriched for melanocyte stem-cell-like signatures, while negatively enriched for interferon and immune activation signatures.DiscussionTogether, through manipulation of human melanoma cell lines and analysis of single-cell states, our results support opposing roles for STING and AXL in the regulation of antigen-presenting genes and interferon sensitivity and more broadly implicate changes to interferon sensitivity in the dedifferentiation process.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "Carl A. Shirley"
    },
    {
      "name": "Michael B. Wolfe"
    },
    {
      "name": "Karla B. Anaya-Aldrete"
    },
    {
      "name": "Minakshi Nihal"
    },
    {
      "name": "Gagan Chhabra"
    },
    {
      "name": "Sean J. McIlwain"
    },
    {
      "name": "Julia M. Krien"
    },
    {
      "name": "Mary A. Ndiaye"
    },
    {
      "name": "Nihal Ahmad"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ef4429tx2fzy4.bib",
  "cited_by": 0,
  "doi": "10.3389/fonc.2026.1946947",
  "fulltext_url": null,
  "id": "ef4429tx2fzy4",
  "issns": [
    "2234-943X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1946947",
  "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": [
    [
      "feed-journal",
      "medicine/oncology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-05",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/ef4429tx2fzy4.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T06:20:20Z",
      "native_id": "10.3389/fonc.2026.1946947",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1946947"
    },
    {
      "first_seen": "2026-11-05T12:21:27Z",
      "native_id": "10.3389/fonc.2026.1946947",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1946947/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "feed-journal:medicine/oncology",
      "subfield": "oncology"
    }
  ],
  "title": "STING signaling opposes AXL to regulate interferon responses in dedifferentiated human melanoma",
  "title_text": "STING signaling opposes AXL to regulate interferon responses in dedifferentiated human melanoma",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T00:21:24Z",
  "url": "https://research.draconitic.com/paper/ef4429tx2fzy4",
  "venue": "Frontiers in Oncology",
  "versions": []
}