{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:03:30Z","timestamp":1791914610071,"version":"4.3.4"},"reference-count":69,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"815","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,9,10]]},"abstract":"<jats:p>\n            Triple-negative breast cancers (TNBCs) lack predictive biomarkers to guide immunotherapy, especially during early-stage disease. To address this issue, we used single-cell RNA sequencing, bulk transcriptomics, and pathology assays on samples from 171 patients with early-stage TNBC receiving chemotherapy with or without immunotherapy. Our investigation identified an enriched subset of interferon (IFN)\u2013induced CD8\n            <jats:sup>+<\/jats:sup>\n            T cells in early TNBC samples, which predict immunotherapy nonresponsiveness. Mechanistically, IFN produced by HLA-DR\n            <jats:sup>+<\/jats:sup>\n            monocytes triggered cellular senescence in CD8\n            <jats:sup>+<\/jats:sup>\n            T cells, which was marked by excessive NAD\n            <jats:sup>+<\/jats:sup>\n            consumption, reduced cytotoxicity, and immunotherapy nonresponsiveness. Nicotinamide mononucleotide treatment restored the function of IFN-induced senescent CD8\n            <jats:sup>+<\/jats:sup>\n            T cells and enhanced immunotherapy efficacy in patient-derived organoid\u2013T cell coculture and in mouse models. Overall, our study identifies IFN-induced T cell senescence as a driver of immunotherapy nonresponsiveness in early TNBC and provides a strategy to restore CD8\n            <jats:sup>+<\/jats:sup>\n            T cell function for immunotherapeutic benefit.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adj7808","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T17:58:14Z","timestamp":1757527094000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":26,"title":["Interferon-induced senescent CD8\n            <sup>+<\/sup>\n            T cells reduce anti-PD1 immunotherapy efficacy in early triple-negative breast cancer"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1569-5111","authenticated-orcid":true,"given":"Tong","family":"Fu","sequence":"first","affiliation":[{"name":"Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, Shanghai 200032, P. 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