{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:26:12Z","timestamp":1792801572183,"version":"4.5.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"vor","delay-in-days":35,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Foundation of Science Technology Department of Zhejiang Province","award":["LKLY25H160006"],"award-info":[{"award-number":["LKLY25H160006"]}],"id":[{"id":"https:\/\/ror.org\/05yj3y977","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Foundation of Science Technology Department of Zhejiang Province","award":["LKLY25H160010"],"award-info":[{"award-number":["LKLY25H160010"]}],"id":[{"id":"https:\/\/ror.org\/05yj3y977","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Foundation of Science Technology Department of Zhejiang Province","award":["LGD22H140003"],"award-info":[{"award-number":["LGD22H140003"]}],"id":[{"id":"https:\/\/ror.org\/05yj3y977","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Zhejiang Health Science and Technology Project","award":["2023KY385"],"award-info":[{"award-number":["2023KY385"]}]},{"name":"Zhejiang Provincial Traditional Chinese Medicine Science and Technology Plan Project","award":["2023ZL733"],"award-info":[{"award-number":["2023ZL733"]}]},{"name":"Shaoxing Health Science and Technology Project","award":["2022KY080"],"award-info":[{"award-number":["2022KY080"]}]},{"name":"Foundation of Science Technology Department of Hangzhou City","award":["2024SZRYBC080002"],"award-info":[{"award-number":["2024SZRYBC080002"]}]},{"name":"Key R&D Program of Hangzhou Science and Technology Bureau","award":["20241203A11"],"award-info":[{"award-number":["20241203A11"]}]},{"name":"Construction Fund of Key Medical Disciplines of Hangzhou-Laboratory Diagnostics","award":["2025HZZD01"],"award-info":[{"award-number":["2025HZZD01"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82470182"],"award-info":[{"award-number":["82470182"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Exp Clin Cancer Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Oncolytic vaccinia viruses (OVV) demonstrate the capacity to inflame the tumor microenvironment (TME) and elicit infiltrating tumor-specific T cells responses. However, OVV treatment paradoxically alters the cancer-immune equilibrium within tumors, attenuating anti-tumor immunity and necessitating a deeper understanding of the viral-induced immune landscape to optimize therapeutic potential. This study investigates the impact of single-domain antibody-armed OVs targeting TIM-3 on TME remodeling, aiming to overcome localized immunosuppression and enhance tumor responsiveness to immunotherapeutic interventions. We engineered a tumor-selective OVV vector encoding single-domain antibodies against murine (mNbTIM3) or human (hNbTIM3) TIM-3. The therapeutic efficacy of OVV-mNbTIM3 was evaluated across multiple murine cancer models, demonstrating that localized V\n                    <jats:sub>HH<\/jats:sub>\n                    TIM3 delivery via OVV-mNbTIM3 promotes systemic anti-tumor immunity in established cancers. Mechanistically, OVV-mNbTIM3 treatment enhances DCs maturation and tumor-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells activation. Notably, intratumoral expression of hNbTIM3 also conferred therapeutic benefit in humanized mice bearing patient-derived cancer xenografts. These findings provide mechanistic insights for enhancing OVV combination therapies and inform the rational design of next-generation oncolytic viruses with engineered immunomodulatory properties.\n                  <\/jats:p>","DOI":"10.1186\/s13046-025-03596-0","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T11:44:30Z","timestamp":1764071070000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["TIM-3 blockade reverses oncolytic vaccinia virus-induced DCs inactivation and T cells exhaustion to improve antitumor immunity and therapeutic efficacy"],"prefix":"10.1186","volume":"44","author":[{"given":"Peipei","family":"Ye","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongming","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gongqiang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shibing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangmin","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"issue":"7","key":"3596_CR1","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1016\/j.cell.2024.02.009","volume":"187","author":"C Swanton","year":"2024","unstructured":"Swanton C, Bernard E, Abbosh C, Andre F, Auwerx J, Balmain A, et al. Embracing cancer complexity: hallmarks of systemic disease. Cell. 2024;187(7):1589\u2013616.","journal-title":"Cell"},{"issue":"4","key":"3596_CR2","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1038\/s41587-025-02629-5","volume":"43","author":"M Tarannum","year":"2025","unstructured":"Tarannum M, Ding X, Barisa M, Hu S, Anderson J, Romee R, et al. Engineering innate immune cells for cancer immunotherapy. Nat Biotechnol. 2025;43(4):516\u201333.","journal-title":"Nat Biotechnol"},{"issue":"4","key":"3596_CR3","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/s41568-024-00785-5","volume":"25","author":"C Luri-Rey","year":"2025","unstructured":"Luri-Rey C, Teijeira A, Wculek SK, de Andrea C, Herrero C, Lopez-Janeiro A, et al. Cross-priming in cancer immunology and immunotherapy. Nat Rev Cancer. 2025;25(4):249\u201373.","journal-title":"Nat Rev Cancer"},{"issue":"1","key":"3596_CR4","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1186\/s12943-024-02179-5","volume":"23","author":"J Wei","year":"2024","unstructured":"Wei J, Li W, Zhang P, Guo F, Liu M. Current trends in sensitizing immune checkpoint inhibitors for cancer treatment. Mol Cancer. 2024;23(1):279.","journal-title":"Mol Cancer"},{"issue":"3","key":"3596_CR5","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/s41571-018-0142-8","volume":"16","author":"JS O\u2019Donnell","year":"2019","unstructured":"O\u2019Donnell JS, Teng MWL, Smyth MJ. Cancer immunoediting and resistance to T cell-based immunotherapy. Nat Rev Clin Oncol. 2019;16(3):151\u201367.","journal-title":"Nat Rev Clin Oncol"},{"issue":"8062","key":"3596_CR6","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/s41586-025-08717-5","volume":"641","author":"Y Shen","year":"2025","unstructured":"Shen Y, Bai X, Zhang Q, Liang X, Jin X, Zhao Z, et al. Oncolytic virus VG161 in refractory hepatocellular carcinoma. Nature. 2025;641(8062):503\u201311.","journal-title":"Nature"},{"issue":"3","key":"3596_CR7","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1038\/s41571-022-00719-w","volume":"20","author":"SZ Shalhout","year":"2023","unstructured":"Shalhout SZ, Miller DM, Emerick KS, Kaufman HL. Therapy with oncolytic viruses: progress and challenges. Nat Rev Clin Oncol. 2023;20(3):160\u201377.","journal-title":"Nat Rev Clin Oncol"},{"key":"3596_CR8","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-009473","author":"Z Li","year":"2024","unstructured":"Li Z, Li M, Yang L, Chen J, Ye Q, Qian W, et al. Oncolytic vaccinia virus armed with anti-CD47 nanobody elicit potent antitumor effects on multiple tumor models via enhancing innate and adoptive immunity. J Immunother Cancer. 2024. https:\/\/doi.org\/10.1136\/jitc-2024-009473.","journal-title":"J Immunother Cancer"},{"issue":"1","key":"3596_CR9","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s12943-024-01946-8","volume":"23","author":"M Toulmonde","year":"2024","unstructured":"Toulmonde M, Guegan JP, Spalato-Ceruso M, Peyraud F, Kind M, Vanhersecke L, et al. Reshaping the tumor microenvironment of cold soft-tissue sarcomas with oncolytic viral therapy: a phase 2 trial of intratumoral JX-594 combined with avelumab and low-dose cyclophosphamide. Mol Cancer. 2024;23(1):38.","journal-title":"Mol Cancer"},{"issue":"1","key":"3596_CR10","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1186\/s13045-022-01370-9","volume":"15","author":"M Toulmonde","year":"2022","unstructured":"Toulmonde M, Cousin S, Kind M, Guegan JP, Bessede A, Le Loarer F, et al. Randomized phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced soft-tissue sarcoma. J Hematol Oncol. 2022;15(1):149.","journal-title":"J Hematol Oncol"},{"key":"3596_CR11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1324744","volume":"14","author":"L Xu","year":"2023","unstructured":"Xu L, Sun H, Lemoine NR, Xuan Y, Wang P. Oncolytic vaccinia virus and cancer immunotherapy. Front Immunol. 2023;14:1324744.","journal-title":"Front Immunol"},{"issue":"1","key":"3596_CR12","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-018-0495-7","volume":"7","author":"ZS Guo","year":"2019","unstructured":"Guo ZS, Lu B, Guo Z, Giehl E, Feist M, Dai E, et al. Vaccinia virus-mediated cancer immunotherapy: cancer vaccines and oncolytics. J Immunother Cancer. 2019;7(1):6.","journal-title":"J Immunother Cancer"},{"key":"3596_CR13","doi-asserted-by":"publisher","first-page":"110303","DOI":"10.1016\/j.virol.2024.110303","volume":"602","author":"H Jin","year":"2025","unstructured":"Jin H, Zhao YR, Huang F, Hong Z, Jia XY, Wang H, et al. Vaccinia virus-mediated oncolytic immunotherapy: emerging strategies for gastrointestinal cancer treatment at dawn. Virology. 2025;602:110303.","journal-title":"Virology"},{"issue":"8","key":"3596_CR14","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101686","volume":"5","author":"C Chen","year":"2024","unstructured":"Chen C, Zhao F, Peng J, Zhao D, Xu L, Li H, et al. Soluble Tim-3 serves as a tumor prognostic marker and therapeutic target for CD8(+) T cell exhaustion and anti-PD-1 resistance. Cell Rep Med. 2024;5(8):101686.","journal-title":"Cell Rep Med"},{"key":"3596_CR15","doi-asserted-by":"crossref","unstructured":"Li M, Zhang Y, Zong L, Zhang M, Wang S, Lei W, et al. An oncolytic vaccinia virus expressing anti-CD47 nanobody exerts enhanced antitumor activity by mediating innate and adaptive immune cell infiltration and activation in the lymphoma tumor microenvironment. Haematologica. 2025;110(9):2113\u201328.","DOI":"10.3324\/haematol.2024.286923"},{"key":"3596_CR16","doi-asserted-by":"publisher","first-page":"14754","DOI":"10.1038\/ncomms14754","volume":"8","author":"Z Liu","year":"2017","unstructured":"Liu Z, Ravindranathan R, Kalinski P, Guo ZS, Bartlett DL. Rational combination of oncolytic vaccinia virus and PD-L1 blockade works synergistically to enhance therapeutic efficacy. Nat Commun. 2017;8:14754.","journal-title":"Nat Commun"},{"key":"3596_CR17","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-010341","author":"Y Jia","year":"2025","unstructured":"Jia Y, Wang Y, Zhao G, Yang Y, Yan W, Wang R, et al. Novel oncolytic vaccinia virus armed with interleukin-27 is a potential therapeutic agent for the treatment of murine pancreatic cancer. J Immunother Cancer. 2025. https:\/\/doi.org\/10.1136\/jitc-2024-010341.","journal-title":"J Immunother Cancer"},{"key":"3596_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-024-01259-7","author":"R Rezaei","year":"2024","unstructured":"Rezaei R, Boulton S, Ahmadi M, Petryk J, Da Silva M, Kooshki Zamani N, et al. Antibiotic-mediated selection of randomly mutagenized and cytokine-expressing oncolytic viruses. Nat Biomed Eng. 2024. https:\/\/doi.org\/10.1038\/s41551-024-01259-7.","journal-title":"Nat Biomed Eng"},{"issue":"640","key":"3596_CR19","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abn2231","volume":"14","author":"L Evgin","year":"2022","unstructured":"Evgin L, Kottke T, Tonne J, Thompson J, Huff AL, van Vloten J, et al. Oncolytic virus-mediated expansion of dual-specific CAR T cells improves efficacy against solid tumors in mice. Sci Transl Med. 2022;14(640):eabn2231.","journal-title":"Sci Transl Med"},{"issue":"11","key":"3596_CR20","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1038\/nm.1882","volume":"14","author":"MA Pule","year":"2008","unstructured":"Pule MA, Savoldo B, Myers GD, Rossig C, Russell HV, Dotti G, et al. Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nat Med. 2008;14(11):1264\u201370.","journal-title":"Nat Med"},{"issue":"7","key":"3596_CR21","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1158\/1078-0432.CCR-24-2498","volume":"31","author":"EJ West","year":"2025","unstructured":"West EJ, Sadoun A, Bendjama K, Erbs P, Smolenschi C, Cassier PA, et al. A phase I clinical trial of intrahepatic artery delivery of TG6002 in combination with oral 5-fluorocytosine in patients with liver-dominant metastatic colorectal cancer. Clin Cancer Res. 2025;31(7):1243\u201356.","journal-title":"Clin Cancer Res"},{"key":"3596_CR22","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-002843","author":"S Zuo","year":"2021","unstructured":"Zuo S, Wei M, Xu T, Kong L, He B, Wang S, et al. An engineered oncolytic vaccinia virus encoding a single-chain variable fragment against TIGIT induces effective antitumor immunity and synergizes with PD-1 or LAG-3 blockade. J Immunother Cancer. 2021. https:\/\/doi.org\/10.1136\/jitc-2021-002843.","journal-title":"J Immunother Cancer"},{"key":"3596_CR23","doi-asserted-by":"crossref","unstructured":"DePeaux K, Rivadeneira DB, Lontos K, Dean VG, Gunn WG, Watson MJ, et al. An oncolytic virus-delivered TGFbeta inhibitor overcomes the immunosuppressive tumor microenvironment. J Exp Med. 2023;220(10):e20230053.","DOI":"10.1084\/jem.20230053"},{"issue":"1","key":"3596_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.omton.2023.200758","volume":"32","author":"C Kurokawa","year":"2024","unstructured":"Kurokawa C, Agrawal S, Mitra A, Galvani E, Burke S, Varshine A, et al. Mediation of antitumor activity by AZD4820 oncolytic vaccinia virus encoding IL-12. Mol Ther Oncolytics. 2024;32(1):200758.","journal-title":"Mol Ther Oncolytics"},{"issue":"101","key":"3596_CR25","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adp7302","volume":"9","author":"Z Zhang","year":"2024","unstructured":"Zhang Z, Ren C, Xiao R, Ma S, Liu H, Dou Y, et al. Palmitoylation of TIM-3 promotes immune exhaustion and restrains antitumor immunity. Sci Immunol. 2024;9(101):eadp7302.","journal-title":"Sci Immunol"},{"issue":"1","key":"3596_CR26","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s13046-025-03394-8","volume":"44","author":"S Imani","year":"2025","unstructured":"Imani S, Farghadani R, Roozitalab G, Maghsoudloo M, Emadi M, Moradi A, et al. Reprogramming the breast tumor immune microenvironment: cold-to-hot transition for enhanced immunotherapy. J Exp Clin Cancer Res. 2025;44(1):131.","journal-title":"J Exp Clin Cancer Res"},{"issue":"8","key":"3596_CR27","doi-asserted-by":"publisher","first-page":"2168","DOI":"10.1158\/1078-0432.CCR-20-4405","volume":"27","author":"JJ Harding","year":"2021","unstructured":"Harding JJ, Moreno V, Bang YJ, Hong MH, Patnaik A, Trigo J, et al. Blocking TIM-3 in treatment-refractory advanced solid tumors: a phase Ia\/b study of LY3321367 with or without an anti-PD-L1 antibody. Clin Cancer Res. 2021;27(8):2168\u201378.","journal-title":"Clin Cancer Res"},{"issue":"1","key":"3596_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-60463-4","volume":"16","author":"X Zhang","year":"2025","unstructured":"Zhang X, Gao Y, Liao H, Wang W, Yang Z, Cao W, et al. TIM3-blockade synergizes with IL2 in alleviating intra-tumoral CD8(+)T cell exhaustion. Nat Commun. 2025;16(1):5130.","journal-title":"Nat Commun"},{"issue":"7865","key":"3596_CR29","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/s41586-021-03626-9","volume":"595","author":"KO Dixon","year":"2021","unstructured":"Dixon KO, Tabaka M, Schramm MA, Xiao S, Tang R, Dionne D, et al. TIM-3 restrains anti-tumour immunity by regulating inflammasome activation. Nature. 2021;595(7865):101\u20136.","journal-title":"Nature"},{"key":"3596_CR30","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-008431","author":"S Wang","year":"2024","unstructured":"Wang S, Li Y, Xu C, Dong J, Wei J. An oncolytic vaccinia virus encoding hyaluronidase reshapes the extracellular matrix to enhance cancer chemotherapy and immunotherapy. J Immunother Cancer. 2024. https:\/\/doi.org\/10.1136\/jitc-2023-008431.","journal-title":"J Immunother Cancer"},{"issue":"1","key":"3596_CR31","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2024.2322173","volume":"13","author":"W Wei","year":"2024","unstructured":"Wei W, Tian L, Zheng X, Zhong L, Chen Y, Dong H, et al. Expression of GPX4 by oncolytic vaccinia virus can significantly enhance CD8(+)T cell function and its impact against pancreatic ductal adenocarcinoma. Oncoimmunology. 2024;13(1):2322173.","journal-title":"Oncoimmunology"},{"issue":"5","key":"3596_CR32","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1158\/2326-6066.CIR-13-0171","volume":"2","author":"IP da Silva","year":"2014","unstructured":"da Silva IP, Gallois A, Jimenez-Baranda S, Khan S, Anderson AC, Kuchroo VK, et al. Reversal of NK-cell exhaustion in advanced melanoma by Tim-3 blockade. Cancer Immunol Res. 2014;2(5):410\u201322.","journal-title":"Cancer Immunol Res"},{"issue":"7","key":"3596_CR33","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1097\/CM9.0000000000003585","volume":"138","author":"X Zhang","year":"2025","unstructured":"Zhang X, He J, Shao Y. Research progress and development potential of oncolytic vaccinia virus. Chin Med J Engl. 2025;138(7):777\u201391.","journal-title":"Chin Med J Engl"},{"key":"3596_CR34","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-004762","author":"F Ju","year":"2022","unstructured":"Ju F, Luo Y, Lin C, Jia X, Xu Z, Tian R, et al. Oncolytic virus expressing PD-1 inhibitors activates a collaborative intratumoral immune response to control tumor and synergizes with CTLA-4 or TIM-3 blockade. J Immunother Cancer. 2022. https:\/\/doi.org\/10.1136\/jitc-2022-004762.","journal-title":"J Immunother Cancer"},{"key":"3596_CR35","doi-asserted-by":"crossref","unstructured":"Sun F, Guo ZS, Gregory AD, Shapiro SD, Xiao G, Qu Z. Dual but not single PD-1 or TIM-3 Blockade enhances oncolytic virotherapy in refractory lung cancer. J Immunother Cancer. 2020;8(1):e000294.","DOI":"10.1136\/jitc-2019-000294"},{"issue":"2","key":"3596_CR36","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.cell.2023.12.011","volume":"187","author":"Y Shapir Itai","year":"2024","unstructured":"Shapir Itai Y, Barboy O, Salomon R, Bercovich A, Xie K, Winter E, et al. Bispecific dendritic-T cell engager potentiates anti-tumor immunity. Cell. 2024;187(2):375\u201389. e18.","journal-title":"Cell"}],"container-title":["Journal of Experimental &amp; Clinical Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13046-025-03596-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13046-025-03596-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13046-025-03596-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T02:21:55Z","timestamp":1767061315000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13046-025-03596-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,25]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3596"],"URL":"https:\/\/doi.org\/10.1186\/s13046-025-03596-0","relation":{},"ISSN":["1756-9966"],"issn-type":[{"value":"1756-9966","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,25]]},"assertion":[{"value":"11 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal procedures and experiments were performed following the guidelines that had been approved by the Animal Care and Use Committee of Zhejiang Provincial People\u2019s Hospital (A202100057).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors contributed to and have approved the manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"333"}}