{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:29:38Z","timestamp":1790882978940,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T00:00:00Z","timestamp":1733875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Our previous studies showed HMGB3 expression may correlate with immunotherapy efficacy in breast cancer patients. Here, we investigated whether HMGB3 overexpression has an impact on anti\u2010PD\u20101 therapy in triple\u2010negative breast cancer (TNBC) and its molecular mechanisms. Animal models were established to observe the effect of HMGB3 on sensitivity to anti\u2010PD\u20101 treatment. Correlation of HMGB3 expression and ferroptosis preventive proteins in TNBC patients' tissues with anti\u2010PD\u20101 therapy efficacy was analyzed. The impact of HMGB3 on IFN\u2010\u03b3 (Interferon\u2010gamma) inhibitory effects and signaling was examined in human TNBC cells where HMGB3 expression was knocked down using siRNA. Moreover, TNBC cells stably transfected with lentiviral vectors containing cDNA of HMGB3 were also used to confirm the effect of overexpression of HMGB3 on IFN\u2010\u03b3 inhibitory effect and signaling. Effect of HMGB3 on IFN\u2010\u03b3\u2010driven ferroptosis and ferroptosis\u2010associated protein expression were also investigated. Correlation of HMGB3 and IRF1 and GPX4 expression in patient's cancer tissue were also investigated. Our results demonstrated that HMGB3 expression contributes to resistance to anti\u2010PD\u20101 therapy in vivo. HMGB3 expression correlated with treatment efficacy of immunotherapy and survival in TNBC patients. HMGB3 silence decreased resistance of breast cancer cells to IFN\u2010\u03b3 cytotoxic effect, while HMGB3 overexpression increased resistance of these cancer cells. HMGB3 silence increased STAT1 phosphorylation and IRF1 expression upon IFN\u2010\u03b3 treatment compared with control. Overexpression of HMGB3 inhibited STAT1 phosphorylation and IFN\u2010\u03b3 signaling in TNBC cells. Moreover, HMGB3 also increased STAT3 activation and had an effect of interaction between STAT1 and STAT3. HMGB3 overexpression decreased IFN\u2010\u03b3\u2010driven ferroptosis in TNBC cells. HMGB3 increased ferroptosis\u2010inhibitory proteins (SLC7A11, GPX4, and SLC3A2) expression in TNBC cells. Ferroptosis inhibition recovers resistance to anti\u2010PD\u20101 therapy in vivo. Immunohistochemistry showed HMGB3 expression correlated with ferroptosis\u2010associated proteins and IRF1 expression in breast cancer tissue. HMGB3 contributes to anti\u2010PD\u20101 resistance by inhibiting IFN\u2010\u03b3\u2010driven ferroptosis in TNBC which suggested HMGB3 is a potential co\u2010target with anti\u2010PD\u20101 therapy for TNBC.<\/jats:p>","DOI":"10.1002\/mc.23861","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T19:02:34Z","timestamp":1733943754000},"page":"490-501","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["HMGB3 Contributes to Anti\u2010PD\u20101 Resistance by Inhibiting IFN\u2010\u03b3\u2010Driven Ferroptosis in TNBC"],"prefix":"10.1002","volume":"64","author":[{"given":"Bo","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Radiotherapy Center, Hubei Cancer Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"Hubei Provincial Clinical Research Center for Breast Cancer Wuhan Hubei China"},{"name":"Wuhan Clinical 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