{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T09:15:44Z","timestamp":1782206144729,"version":"3.54.5"},"reference-count":55,"publisher":"American Association for the Advancement of Science (AAAS)","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473956"],"award-info":[{"award-number":["82473956"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["spj.science.org"],"crossmark-restriction":true},"short-container-title":["Research"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n            A promising therapeutic approach in oncology involves immune checkpoint blockade (ICB), which stimulates anti-tumor immune responses. Nevertheless, the effectiveness of this treatment in clinical settings remains limited, underscoring the need for complementary strategies. Recent studies highlight the potential of type I interferon (IFN-I) inducers to reprogram the tumor microenvironment and enhance ICB outcomes. Herein, through high-content screening of a natural compound library, we identified daurisoline (DS), a bioactive alkaloid extracted from the Chinese herbal medicine Rhizoma Menispermi, as a potent inducer of IFN-I signaling. Our findings indicated that DS up-regulates interferon responses and pro-inflammatory cytokine expression in a TANK-binding kinase 1 (TBK1)-dependent manner. In\u00a0vivo, DS exhibited marked tumor growth inhibition by activating dendritic cells, macrophages, and CD8\n            <jats:sup>+<\/jats:sup>\n            T cells, thereby enhancing anti-tumor immunity. Utilizing the LiP-SMap approach, we identified low-density lipoprotein receptor-related protein 1 (LRP1) as the direct target of DS. Mechanistically, the binding of DS to LRP1 substantially disrupted lysosomal function, which subsequently triggered 5\u2032-azacytidine-induced protein 2-mediated TBK1 activation and IFN-I production. Furthermore, DS demonstrated synergistic effects with anti-programmed death 1 therapy and a stimulator of interferon genes agonist by remodeling the immunosuppressive microenvironment. Collectively, our findings establish LRP1 as a novel therapeutic target for cancer immunotherapy and highlight DS-driven immune reprogramming as a translatable strategy to potentiate ICB efficacy.\n          <\/jats:p>","DOI":"10.34133\/research.0764","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T11:19:01Z","timestamp":1749813541000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":2,"title":["Daurisoline Modulates the TBK1-Dependent Type I Interferon Pathway to Boost Anti-tumor Immunity via Targeting of LRP1"],"prefix":"10.34133","volume":"8","author":[{"given":"Borui","family":"Tang","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, \rCapital Medical University, Beijing 100069, China."},{"name":"National Institute for Drug Clinical Trial, Beijing Tongren Hospital, \rCapital Medical University, Beijing 100005, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology, \rChinese Academy of Medical Sciences &amp; 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