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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\n                  <jats:italic>BLTP3A<\/jats:italic>\n                  M1098T increases stress-induced lysosomal damage. Patients carrying M1098T had longer overall survival and tumors enriched for cytotoxic T cell\u2013myeloid neighborhoods. In syngeneic tumors,\n                  <jats:italic>Bltp3a<\/jats:italic>\n                  loss or orthologous variant expression delayed progression and generated\n                  <jats:italic>Cxcl9<\/jats:italic>\n                  + 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\u2013ATF4\u2013BLTP3A feedback program. BLTP3A dysfunction disrupted CASM-associated lysosomal stress resolution, resulting in prolonged STING activity and sustained tumor-derived IFN-\u03bb without increased cGAMP. Tumor-cell STING and IFN-\u03bb 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.\n                <\/jats:p>","DOI":"10.64898\/2026.09.25.752224","type":"posted-content","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:40:26Z","timestamp":1790606426000},"source":"Crossref","is-referenced-by-count":0,"title":["BLTP3A dysfunction unleashes lysosomal stress\u2013induced antitumor immunity through STING"],"prefix":"10.64898","author":[{"given":"Elaheh S.","family":"Hosseini","sequence":"first","affiliation":[{"name":"Duncan and Nancy MacMillan Cancer Immunology and Metabolism Center of Excellence, Rutgers Cancer Institute, New Brunswick, New Jersey"},{"name":"Rutgers School of Graduate Studies, Rutgers University, New Brunswick, New 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