{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:28:25Z","timestamp":1792787305720,"version":"4.5.0"},"reference-count":48,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["8267113332"],"award-info":[{"award-number":["8267113332"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["82572106"],"award-info":[{"award-number":["82572106"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["82302073"],"award-info":[{"award-number":["82302073"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515011033"],"award-info":[{"award-number":["2023A1515011033"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023M743997"],"award-info":[{"award-number":["2023M743997"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangdong Major Project of Basic Research","award":["2023B0303000018"],"award-info":[{"award-number":["2023B0303000018"]}]},{"name":"Guangdong Province Youth Top Talent Special Pillar Program","award":["2024"],"award-info":[{"award-number":["2024"]}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022B1515020023"],"award-info":[{"award-number":["2022B1515020023"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2314050001076"],"award-info":[{"award-number":["2314050001076"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010256","name":"Guangzhou Municipal Science and Technology Project","doi-asserted-by":"publisher","award":["2025B03J0063, 2024A04J6556"],"award-info":[{"award-number":["2025B03J0063, 2024A04J6556"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key R&D Program of China","award":["2021YFA1302000"],"award-info":[{"award-number":["2021YFA1302000"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,9,9]]},"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Combining immunotherapy with endocrine therapy and\/or chemotherapy promotes prognosis in patients with estrogen receptor-positive\/HER2-negative (ER\n                      <jats:sup>+<\/jats:sup>\n                      HER2\n                      <jats:sup>\u2212<\/jats:sup>\n                      ) breast cancer; however, the unclear underlying mechanisms limit their widespread application in clinical practice. This study aimed to investigate how ER signaling regulates antitumor immunity and influences responses to chemoimmunotherapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We evaluated pathological complete response rates between ER-positive and ER-negative breast cancer patients across internal and external cohorts treated with immunotherapy and neoadjuvant chemotherapy. Mechanistic studies were conducted to explore the crosstalk between ER and immunogenic cell death (ICD) through high mobility group box 1 (HMGB1) SUMOylation. The therapeutic potential of chemoimmunotherapy regimens was assessed using immunocompetent mouse models of ER\n                      <jats:sup>+<\/jats:sup>\n                      breast cancer.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Patients with ER\n                      <jats:sup>\u2212<\/jats:sup>\n                      breast cancer had higher pathological complete response rates after immunotherapy and neoadjuvant chemotherapy compared with those with ER\n                      <jats:sup>+<\/jats:sup>\n                      breast cancer in both internal and external cohorts. Enhanced immune responses were observed in ER\n                      <jats:sup>\u2212<\/jats:sup>\n                      breast cancer after chemotherapy, which was attributed to the induction of ICD via the release of HMGB1. Mechanistically, ER inhibits HMGB1 release by directly interacting with the HMG Box B domain and suppressing its SUMOylation at the K114 site, thereby suppressing the antitumor immune response.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Therapeutically, combining ER antagonist with chemotherapy potentiated the efficacy of PD-1 blockade through HMGB1 in an immunocompetent mice model. These findings provide new mechanistic insights and clinical strategies for addressing immunotherapy resistance in ER\n                      <jats:sup>+<\/jats:sup>\n                      breast cancer patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-014506","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:39:31Z","timestamp":1790861971000},"page":"e014506","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Hormone therapy potentiates chemoimmunotherapy by inducing SUMOylation-mediated immunogenic cell death"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct04109066","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03725059","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02990845","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Jiaqian","family":"Li","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China"},{"name":"Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhu","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China"},{"name":"Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China"},{"name":"Guangdong Provincial Key Laboratory of Liver Disease Research, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China"},{"name":"Breast Cancer Center and Department of Thyroid and Breast Surgery, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunping","family":"Wei","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China"},{"name":"Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Liver Disease Research, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China"},{"name":"Department of Infectious Diseases, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Wen","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Liver Disease Research, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China"},{"name":"Department of Infectious Diseases, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China"},{"name":"Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0649-0437","authenticated-orcid":false,"given":"Qiyi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Liver Disease Research, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China"},{"name":"Department of Infectious Diseases, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China"},{"name":"Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"2026100106150661000_14.10.e014506.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0488-6"},{"key":"2026100106150661000_14.10.e014506.2","doi-asserted-by":"crossref","DOI":"10.1186\/s13045-024-01649-z","article-title":"Current and future immunotherapy for breast cancer","volume":"17","author":"Heater","year":"2024","journal-title":"J Hematol Oncol"},{"key":"2026100106150661000_14.10.e014506.3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.64.8931"},{"key":"2026100106150661000_14.10.e014506.4","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-022-11578-x","article-title":"Immunological profiles of the breast cancer microenvironment represented by tumor-infiltrating lymphocytes and PD-L1 expression","volume":"12","author":"Hanamura","year":"2022","journal-title":"Sci Rep"},{"key":"2026100106150661000_14.10.e014506.5","doi-asserted-by":"crossref","unstructured":"Cardoso FC , McArthur HL , Schmid P , et al . LBA21 keynote-756: phase III study of neoadjuvant pembrolizumab (Pembro) or placebo (Pbo) + chemotherapy (Chemo), followed by adjuvant Pembro or Pbo + endocrine therapy (ET) for early-stage high-risk ER+\/HER2\u2013 breast cancer. Ann Oncol 2023.","DOI":"10.1016\/j.annonc.2023.10.011"},{"key":"2026100106150661000_14.10.e014506.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.10.010"},{"key":"2026100106150661000_14.10.e014506.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03415-7"},{"key":"2026100106150661000_14.10.e014506.8","doi-asserted-by":"crossref","DOI":"10.1016\/j.xcrm.2024.101879","article-title":"Hormone therapy enhances anti-PD1 efficacy in premenopausal estrogen receptor-positive and HER2-negative advanced breast cancer","volume":"6","author":"Chen","year":"2025","journal-title":"Cell Rep Med"},{"key":"2026100106150661000_14.10.e014506.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-018-0007-y"},{"key":"2026100106150661000_14.10.e014506.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-021-00347-z"},{"key":"2026100106150661000_14.10.e014506.11","doi-asserted-by":"crossref","DOI":"10.1038\/s41392-024-01979-x","article-title":"Cold and hot tumors: from molecular mechanisms to targeted therapy","volume":"9","author":"Wu","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"2026100106150661000_14.10.e014506.12","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801005"},{"key":"2026100106150661000_14.10.e014506.13","doi-asserted-by":"crossref","unstructured":"Yang D , Wang Y , Pattarayan D , et al . Systematic investigation of chemo-immunotherapy synergism to shift anti-PD-1 resistance in cancer. In Review [Preprint] 2023. doi:10.21203\/rs.3.rs-3290264\/v1","DOI":"10.21203\/rs.3.rs-3290264\/v1"},{"key":"2026100106150661000_14.10.e014506.14","doi-asserted-by":"publisher","DOI":"10.1210\/me.2004-0486"},{"key":"2026100106150661000_14.10.e014506.15","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2019.1703449","article-title":"Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology","volume":"9","author":"Vanmeerbeek","year":"2020","journal-title":"Oncoimmunology"},{"key":"2026100106150661000_14.10.e014506.16","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-024-00920-9"},{"key":"2026100106150661000_14.10.e014506.17","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050915"},{"key":"2026100106150661000_14.10.e014506.18","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2019-000337","article-title":"Consensus guidelines for the definition, detection and interpretation of immunogenic cell death","volume":"8","author":"Galluzzi","year":"2020","journal-title":"J Immunother Cancer"},{"key":"2026100106150661000_14.10.e014506.19","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-100008"},{"key":"2026100106150661000_14.10.e014506.20","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01132-2"},{"key":"2026100106150661000_14.10.e014506.21","doi-asserted-by":"crossref","DOI":"10.1186\/s12967-023-04017-6","article-title":"Immunogenic cell death in cancer: concept and therapeutic implications","volume":"21","author":"Galluzzi","year":"2023","journal-title":"J Transl Med"},{"key":"2026100106150661000_14.10.e014506.22","doi-asserted-by":"crossref","DOI":"10.1038\/s41419-020-03221-2","article-title":"Detection of immunogenic cell death and its relevance for cancer therapy","volume":"11","author":"Fucikova","year":"2020","journal-title":"Cell Death Dis"},{"key":"2026100106150661000_14.10.e014506.23","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-1209"},{"key":"2026100106150661000_14.10.e014506.24","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-023-02181-6"},{"key":"2026100106150661000_14.10.e014506.25","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1038\/s43018-024-00734-z","article-title":"Modeling T cell temporal response to cancer immunotherapy rationalizes development of combinatorial treatment protocols","volume":"5","author":"Barboy","year":"2024","journal-title":"Nat Cancer"},{"key":"2026100106150661000_14.10.e014506.26","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)66546-4"},{"key":"2026100106150661000_14.10.e014506.27","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2015.99"},{"key":"2026100106150661000_14.10.e014506.28","doi-asserted-by":"crossref","DOI":"10.1172\/JCI183656","article-title":"MAP3K1 mutations confer tumor immune heterogeneity in hormone receptor-positive HER2-negative breast cancer","volume":"135","author":"Cai","year":"2024","journal-title":"J Clin Invest"},{"key":"2026100106150661000_14.10.e014506.29","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4491"},{"key":"2026100106150661000_14.10.e014506.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.10.012"},{"key":"2026100106150661000_14.10.e014506.31","doi-asserted-by":"publisher","DOI":"10.1038\/nm1523"},{"key":"2026100106150661000_14.10.e014506.32","doi-asserted-by":"crossref","DOI":"10.1001\/jamaoncol.2017.2085","article-title":"Role of Cytotoxic Tumor-Infiltrating Lymphocytes in Predicting Outcomes in Metastatic HER2-Positive Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial","volume":"3","author":"Liu","year":"2017","journal-title":"JAMA Oncol"},{"key":"2026100106150661000_14.10.e014506.33","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3258"},{"key":"2026100106150661000_14.10.e014506.34","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-100311-102839"},{"key":"2026100106150661000_14.10.e014506.35","doi-asserted-by":"publisher","DOI":"10.1038\/nm1622"},{"key":"2026100106150661000_14.10.e014506.36","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2617"},{"key":"2026100106150661000_14.10.e014506.37","doi-asserted-by":"publisher","DOI":"10.1038\/nature10098"},{"key":"2026100106150661000_14.10.e014506.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.06.020"},{"key":"2026100106150661000_14.10.e014506.39","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070247"},{"key":"2026100106150661000_14.10.e014506.40","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2017.133"},{"key":"2026100106150661000_14.10.e014506.41","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-022-00736-w"},{"key":"2026100106150661000_14.10.e014506.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2025.09.003"},{"key":"2026100106150661000_14.10.e014506.43","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1910549"},{"key":"2026100106150661000_14.10.e014506.44","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-1705"},{"key":"2026100106150661000_14.10.e014506.45","doi-asserted-by":"crossref","DOI":"10.1186\/s12935-021-02003-w","article-title":"Estrogen\/ER in anti-tumor immunity regulation to tumor cell and tumor microenvironment","volume":"21","author":"Wang","year":"2021","journal-title":"Cancer Cell Int"},{"key":"2026100106150661000_14.10.e014506.46","doi-asserted-by":"crossref","DOI":"10.1002\/advs.202002500","article-title":"Nidogen-1 Mitigates Ischemia and Promotes Tissue Survival and Regeneration","volume":"8","author":"Zbinden","year":"2021","journal-title":"Adv Sci (Weinh)"},{"key":"2026100106150661000_14.10.e014506.47","doi-asserted-by":"crossref","DOI":"10.1002\/advs.202202956","article-title":"Tumor Cell-Intrinsic CD96 Mediates Chemoresistance and Cancer Stemness by Regulating Mitochondrial Fatty Acid \u03b2-Oxidation","volume":"10","author":"Li","year":"2023","journal-title":"Adv Sci (Weinh)"},{"key":"2026100106150661000_14.10.e014506.48","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/s43018-022-00352-7","article-title":"Concurrent delivery of immune checkpoint blockade modulates T cell dynamics to enhance neoantigen vaccine-generated antitumor immunity","volume":"3","author":"Liu","year":"2022","journal-title":"Nat Cancer"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2025-014506","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:39:36Z","timestamp":1790861976000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2025-014506"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":48,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,10,1]]},"published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1136\/jitc-2025-014506"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2025-014506","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]}}}