{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:33:48Z","timestamp":1792787628228,"version":"4.5.0"},"reference-count":74,"publisher":"American Society for Clinical Investigation","issue":"20","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":51,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["No. 82373005"],"award-info":[{"award-number":["No. 82373005"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Special Foundation for Taishan Scholars","award":["No. tstp20250509"],"award-info":[{"award-number":["No. tstp20250509"]}]},{"name":"National Natural Science Foundation of China","award":["No. 82303814"],"award-info":[{"award-number":["No. 82303814"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Shandong Provincial Natural Science Foundation, China","award":["No. ZR2023QH307"],"award-info":[{"award-number":["No. ZR2023QH307"]}]},{"name":"Shandong Provincial Natural Science Foundation, China","award":["No. ZR2025MS1262"],"award-info":[{"award-number":["No. ZR2025MS1262"]}]},{"name":"National Natural Science Foundation of China","award":["No. 82373267"],"award-info":[{"award-number":["No. 82373267"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["No. 82573211"],"award-info":[{"award-number":["No. 82573211"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,15]]},"abstract":"<jats:p>\n                    Triple-negative breast cancer (TNBC), characterized by aggressive behavior and poor prognosis, presents a formidable clinical challenge. Despite guideline endorsement of chemoimmunotherapy as a standard treatment in TNBC, durable responses remain rare, largely due to an immunologically \u201ccold\u201d tumor microenvironment (TME). Through integrated analysis, we identified the F-box protein FBXW5 as a tumor-intrinsic immunosuppressive regulator, whose expression is elevated in immunologically \u201ccold\u201d TNBC and correlates with dismal patient survival. Genetic knockdown of murine\n                    <jats:italic>Fbxw5<\/jats:italic>\n                    suppressed tumor growth, reinvigorated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u2013mediated antitumor immunity, and sensitized TNBC tumors to both single-agent and combined chemoimmunotherapy in preclinical models. Mechanistically, FBXW5 acts within the SKP1\/CUL1\/F-box protein E3 ligase complex to bind RIGI and MDA5, promoting their K27-linked polyubiquitination and subsequent SQSTM1-mediated autophagic degradation. This process blunts cytosolic RNA sensing and type I interferon signaling, thereby limiting CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration and activation. Our findings establish FBXW5 as a master regulator of the \u201ccold\u201d TME, presenting a potential predictive biomarker and actionable therapeutic target for enhancing chemoimmunotherapy in TNBC.\n                  <\/jats:p>","DOI":"10.1172\/jci201573","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T16:01:21Z","timestamp":1787673681000},"source":"Crossref","is-referenced-by-count":0,"title":["FBXW5 blunts RIGI\/MDA5\/IFN signaling to drive immune evasion and chemo-immune resistance in triple-negative breast cancer models"],"prefix":"10.1172","volume":"136","author":[{"given":"Xin","family":"Li","sequence":"first","affiliation":[{"name":"Department of Breast Surgery, General Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, General Surgery, 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