{
  "abstract": "High-grade serous ovarian cancer progresses within a lipid-rich ascites microenvironment that engages stress-adaptation programs supporting malignant growth, yet how failed stress resolution influences tumor progression remains incompletely defined. Here, we show that unresolved lysosomal stress restrains tumor progression by sustaining tumor cell-intrinsic STING activity and reorganizing antitumor immunity. We identify BLTP3A as a lysosomal stress-resolution factor in ovarian cancer and show that the common germline missense variant BLTP3A M1098T increases stress-induced lysosomal damage. Patients carrying M1098T had longer overall survival and tumors enriched for cytotoxic T cell-myeloid neighborhoods. In syngeneic tumors, Bltp3a loss or orthologous variant expression delayed progression and generated Cxcl9+ antigen-presenting macrophage niches; M1098T-expressing human tumors similarly promoted interferon-responsive myeloid and T-cell enrichment in humanized mice. Mechanistically, ascites-induced lysosomal stress activated a STING-ATF4-BLTP3A feedback program. BLTP3A dysfunction disrupted CASM-associated lysosomal stress resolution, resulting in prolonged STING activity and sustained tumor-derived IFN-{lambda} without increased cGAMP. Tumor-cell STING and IFN-{lambda} were required for immune remodeling and tumor control. Thus, BLTP3A-dependent lysosomal stress resolution constrains the persistence of stress-induced STING signaling, whereas failure of this response sustains a tumor-intrinsic inflammatory program that organizes protective antitumor immunity.",
  "abstract_shown": true,
  "affiliations": [
    "Rutgers Cancer Institute"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "name": "E. S. Hosseini"
    },
    {
      "name": "S. Wang"
    },
    {
      "name": "M. Arabzadeh"
    },
    {
      "name": "K. E. Warrington"
    },
    {
      "name": "M. T. Sogaard"
    },
    {
      "name": "A. Singh"
    },
    {
      "name": "W. Chen"
    },
    {
      "name": "L. Ranasinghe"
    },
    {
      "name": "R. Kumari"
    },
    {
      "name": "C. K. Alcott"
    },
    {
      "name": "A. Robinson"
    },
    {
      "name": "S. Yadav"
    },
    {
      "name": "W. Hu"
    },
    {
      "name": "J. Cao"
    },
    {
      "name": "E. Girda"
    },
    {
      "name": "E. P. White"
    },
    {
      "name": "C. S. Hinrichs"
    },
    {
      "affs": [
        0
      ],
      "name": "K. K. Payne"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/77adpmkp76q8p.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.25.752224",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.752224v1.full",
  "id": "77adpmkp76q8p",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.752224v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2403|interferon and immune responses"
    ]
  ],
  "openalex": "W7214668794",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.752224v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/77adpmkp76q8p.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:50Z",
      "native_id": "10.64898/2026.09.25.752224",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.25.752224v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "BLTP3A dysfunction unleashes lysosomal stress-induced antitumor immunity through STING",
  "title_text": "BLTP3A dysfunction unleashes lysosomal stress-induced antitumor immunity through STING",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:50Z",
  "url": "https://research.draconitic.com/paper/77adpmkp76q8p",
  "venue": "bioRxiv",
  "versions": []
}