{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T06:11:14Z","timestamp":1777011074299,"version":"3.51.4"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e9 Paris-Saclay, France"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Immunol Immunother"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The endothelin axis is highly involved and overexpressed in many tumors, making it an interesting therapeutic target. However, except for strategies based on small molecule antagonists, this axis is poorly targeted by immunotherapy approaches. Although cell-based therapies, in particular CAR-T cells, have produced impressive results in treating hematological tumors, they remain challenging for solid tumors. CAR-macrophages represent a promising alternative, but only a few therapeutic targets have been evaluated thus far. Having developed antibodies targeting ET1R, our laboratory proposes this axis as a target for CAR-macrophages development. This study investigated the efficacy of CAR-macrophages directed against the endothelin B receptor (ET\n                    <jats:sub>B<\/jats:sub>\n                    ), expressed by melanoma cells developed from Rendomab B4 (RB4), an antibody targeting ET\n                    <jats:sub>B<\/jats:sub>\n                    . Before assembling the CAR against ET\n                    <jats:sub>B<\/jats:sub>\n                    , the scFv RB4 fragment, derived from the full-length RB4 antibody, was characterized. It exhibited properties similar to those of the original antibody and displayed exclusive recognition of ET\n                    <jats:sub>B<\/jats:sub>\n                    -positive melanoma cell lines. CAR RB4 evaluation showed remarkable antitumor activity against the high ET\n                    <jats:sub>B<\/jats:sub>\n                    -expressing WM266 cell line, but no activity on the low ET\n                    <jats:sub>B<\/jats:sub>\n                    -expressing A375 cell line. We show the first proof of concept for CAR therapy targeting the endothelin axis and establish CAR RB4 as a promising candidate for the treatment of ET\n                    <jats:sub>B<\/jats:sub>\n                    -positive solid tumors.\n                  <\/jats:p>","DOI":"10.1007\/s00262-025-04219-5","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T12:39:38Z","timestamp":1762951178000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Generating CAR-macrophages to target endothelin B receptor-positive tumors"],"prefix":"10.1007","volume":"74","author":[{"given":"Cyril","family":"Lherminier","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narciso","family":"Costa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amaury","family":"Herbet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Hauti\u00e8re","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alo\u00efse","family":"Mabondzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e9r\u00e9mie","family":"Martinet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Didier","family":"Boquet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"4219_CR1","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1038\/nrc3546","volume":"13","author":"L Rosan\u00f2","year":"2013","unstructured":"Rosan\u00f2 L, Spinella F, Bagnato A (2013) Endothelin 1 in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer 13:637\u2013651. https:\/\/doi.org\/10.1038\/nrc3546","journal-title":"Nat Rev Cancer"},{"key":"4219_CR2","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/S1043-2760(98)00094-0","volume":"9","author":"A Bagnato","year":"1998","unstructured":"Bagnato A, Catt KJ (1998) Endothelins as autocrine regulators of tumor cell growth. Trends Endocrinol Metab 9:378\u2013383. https:\/\/doi.org\/10.1016\/S1043-2760(98)00094-0","journal-title":"Trends Endocrinol Metab"},{"key":"4219_CR3","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1080\/19420862.2016.1208865","volume":"8","author":"A Borrull","year":"2016","unstructured":"Borrull A, Allard B, Wijkhuisen A et al (2016) Rendomab B4, a monoclonal antibody that discriminates the human endothelin B receptor of melanoma cells and inhibits their migration. MAbs 8:1371\u20131385. https:\/\/doi.org\/10.1080\/19420862.2016.1208865","journal-title":"MAbs"},{"key":"4219_CR4","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H et al (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74:229\u2013263. https:\/\/doi.org\/10.3322\/caac.21834","journal-title":"CA Cancer J Clin"},{"key":"4219_CR5","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.cpt.2024.08.002","volume":"3","author":"AH Roky","year":"2025","unstructured":"Roky AH, Islam MM, Ahasan AMF et al (2025) Overview of skin cancer types and prevalence rates across continents. Cancer Pathogenesis and Therapy 3:89\u2013100. https:\/\/doi.org\/10.1016\/j.cpt.2024.08.002","journal-title":"Cancer Pathogenesis and Therapy"},{"key":"4219_CR6","first-page":"572","volume":"7","author":"A Sandru","year":"2014","unstructured":"Sandru A, Voinea S, Panaitescu E, Blidaru A (2014) Survival rates of patients with metastatic malignant melanoma. J Med Life 7:572\u2013576","journal-title":"J Med Life"},{"key":"4219_CR7","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1200\/JCO.21.02229","volume":"40","author":"JD Wolchok","year":"2022","unstructured":"Wolchok JD, Chiarion-Sileni V, Gonzalez R et al (2022) Long-term outcomes with nivolumab plus ipilimumab or nivolumab alone versus ipilimumab in patients with advanced melanoma. J Clin Oncol 40:127\u2013137. https:\/\/doi.org\/10.1200\/JCO.21.02229","journal-title":"J Clin Oncol"},{"key":"4219_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/14712598.2025.2485315","volume":"25","author":"LV Maul","year":"2025","unstructured":"Maul LV, Ramelyte Egle, Dummer Reinhard, Mangana J (2025) Management of metastatic melanoma with combinations including PD-1 inhibitors. Expert Opin Biol Ther 25:1\u201312. https:\/\/doi.org\/10.1080\/14712598.2025.2485315","journal-title":"Expert Opin Biol Ther"},{"key":"4219_CR9","doi-asserted-by":"publisher","first-page":"2656","DOI":"10.1200\/JCO.21.00612","volume":"39","author":"AA Sarnaik","year":"2021","unstructured":"Sarnaik AA, Hamid O, Khushalani NI et al (2021) Lifileucel, a tumor-infiltrating lymphocyte therapy, in metastatic melanoma. JCO 39:2656\u20132666. https:\/\/doi.org\/10.1200\/JCO.21.00612","journal-title":"JCO"},{"key":"4219_CR10","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25189848","volume":"25","author":"G Nassief","year":"2024","unstructured":"Nassief G, Anaeme A, Moussa K et al (2024) Recent advancements in cell-based therapies in melanoma. Int J Mol Sci 25:9848. https:\/\/doi.org\/10.3390\/ijms25189848","journal-title":"Int J Mol Sci"},{"key":"4219_CR11","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s13045-021-01067-5","volume":"14","author":"J Edeline","year":"2021","unstructured":"Edeline J, Houot R, Marabelle A, Alcantara M (2021) CAR-T cells and BiTEs in solid tumors: challenges and perspectives. J Hematol Oncol 14:65. https:\/\/doi.org\/10.1186\/s13045-021-01067-5","journal-title":"J Hematol Oncol"},{"key":"4219_CR12","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s13045-018-0568-6","volume":"11","author":"J Li","year":"2018","unstructured":"Li J, Li W, Huang K et al (2018) Chimeric antigen receptor T cell (CAR-T) immunotherapy for solid tumors: lessons learned and strategies for moving forward. J Hematol Oncol 11:22. https:\/\/doi.org\/10.1186\/s13045-018-0568-6","journal-title":"J Hematol Oncol"},{"key":"4219_CR13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41408-021-00459-7","volume":"11","author":"RC Sterner","year":"2021","unstructured":"Sterner RC, Sterner RM (2021) Car-T cell therapy: current limitations and potential strategies. Blood Cancer J 11:1\u201311. https:\/\/doi.org\/10.1038\/s41408-021-00459-7","journal-title":"Blood Cancer J"},{"key":"4219_CR14","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.it.2019.02.003","volume":"40","author":"P Pathria","year":"2019","unstructured":"Pathria P, Louis TL, Varner JA (2019) Targeting tumor-associated macrophages in cancer. Trends Immunol 40:310\u2013327. https:\/\/doi.org\/10.1016\/j.it.2019.02.003","journal-title":"Trends Immunol"},{"key":"4219_CR15","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111605","volume":"139","author":"Y Chen","year":"2021","unstructured":"Chen Y, Yu Z, Tan X et al (2021) CAR-macrophage: a new immunotherapy candidate against solid tumors. Biomed Pharmacother 139:111605. https:\/\/doi.org\/10.1016\/j.biopha.2021.111605","journal-title":"Biomed Pharmacother"},{"key":"4219_CR16","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1038\/s41587-020-0520-5","volume":"38","author":"E Dolgin","year":"2020","unstructured":"Dolgin E (2020) Cancer-eating immune cells kitted out with CARs. Nat Biotechnol 38:509\u2013511. https:\/\/doi.org\/10.1038\/s41587-020-0520-5","journal-title":"Nat Biotechnol"},{"key":"4219_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2024.123300","volume":"361","author":"Y Shi","year":"2025","unstructured":"Shi Y, Li X, Dong Y et al (2025) Exploring the potential of CAR-macrophage therapy. Life Sci 361:123300. https:\/\/doi.org\/10.1016\/j.lfs.2024.123300","journal-title":"Life Sci"},{"key":"4219_CR18","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1038\/sj.gt.3302706","volume":"13","author":"A Biglari","year":"2006","unstructured":"Biglari A, Southgate TD, Fairbairn LJ, Gilham DE (2006) Human monocytes expressing a CEA-specific chimeric CD64 receptor specifically target CEA-expressing tumour cells in vitro and in vivo. Gene Ther 13:602\u2013610. https:\/\/doi.org\/10.1038\/sj.gt.3302706","journal-title":"Gene Ther"},{"key":"4219_CR19","doi-asserted-by":"publisher","first-page":"994","DOI":"10.3390\/cells11060994","volume":"11","author":"D Paasch","year":"2022","unstructured":"Paasch D, Meyer J, Stamopoulou A et al (2022) Ex vivo generation of CAR macrophages from hematopoietic stem and progenitor cells for use in cancer therapy. Cells 11:994. https:\/\/doi.org\/10.3390\/cells11060994","journal-title":"Cells"},{"key":"4219_CR20","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1038\/s41587-020-0462-y","volume":"38","author":"M Klichinsky","year":"2020","unstructured":"Klichinsky M, Ruella M, Shestova O et al (2020) Human chimeric antigen receptor macrophages for cancer immunotherapy. Nat Biotechnol 38:947\u2013953. https:\/\/doi.org\/10.1038\/s41587-020-0462-y","journal-title":"Nat Biotechnol"},{"key":"4219_CR21","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.36688","volume":"7","author":"MA Morrissey","year":"2018","unstructured":"Morrissey MA, Williamson AP, Steinbach AM et al (2018) Chimeric antigen receptors that trigger phagocytosis. Elife 7:e36688. https:\/\/doi.org\/10.7554\/eLife.36688","journal-title":"Elife"},{"key":"4219_CR22","doi-asserted-by":"crossref","unstructured":"Lei A, Hua Y, Lu S, et al 2022 A Chimera Antigen Receptor Containing TLR4 Signaling Domain Enhances CAR-iMACs Polarization and Potency against Solid Tumors","DOI":"10.21203\/rs.3.rs-1279112\/v1"},{"key":"4219_CR23","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1007\/s00262-024-03759-6","volume":"73","author":"K Chupradit","year":"2024","unstructured":"Chupradit K, Muneekaew S, Wattanapanitch M (2024) Engineered CD147-CAR macrophages for enhanced phagocytosis of cancers. Cancer Immunol Immunother 73:170. https:\/\/doi.org\/10.1007\/s00262-024-03759-6","journal-title":"Cancer Immunol Immunother"},{"key":"4219_CR24","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1186\/s12967-023-04479-8","volume":"21","author":"Y Chen","year":"2023","unstructured":"Chen Y, Zhu X, Liu H et al (2023) The application of HER2 and CD47 CAR-macrophage in ovarian cancer. J Transl Med 21:654. https:\/\/doi.org\/10.1186\/s12967-023-04479-8","journal-title":"J Transl Med"},{"key":"4219_CR25","doi-asserted-by":"publisher","first-page":"S257","DOI":"10.33549\/physiolres.933848","volume":"67","author":"A Herbet","year":"2018","unstructured":"Herbet A, Costa N, Leventoux N et al (2018) Antibodies targeting human endothelin-1 receptors reveal different conformational states in cancer cells. Physiol Res 67:S257\u2013S264. https:\/\/doi.org\/10.33549\/physiolres.933848","journal-title":"Physiol Res"},{"key":"4219_CR26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0286056","volume":"18","author":"T Liu","year":"2023","unstructured":"Liu T, Huang T, Li J et al (2023) Optimization of differentiation and transcriptomic profile of THP-1 cells into macrophage by PMA. PLoS ONE 18:e0286056. https:\/\/doi.org\/10.1371\/journal.pone.0286056","journal-title":"PLoS ONE"},{"key":"4219_CR27","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1387\/ijdb.041951rl","volume":"49","author":"R Lahav","year":"2005","unstructured":"Lahav R (2005) Endothelin receptor B is required for the expansion of melanocyte precursors and malignant melanoma. Int J Dev Biol 49:173\u2013180. https:\/\/doi.org\/10.1387\/ijdb.041951rl","journal-title":"Int J Dev Biol"},{"key":"4219_CR28","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1042\/CS20240426","volume":"138","author":"PF Arndt","year":"2024","unstructured":"Arndt PF, Turkowski K, Cekay MJ et al (2024) Endothelin and the tumor microenvironment: a finger in every pie. Clin Sci 138:617\u2013634. https:\/\/doi.org\/10.1042\/CS20240426","journal-title":"Clin Sci"},{"key":"4219_CR29","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1089\/cmb.2019.0197","volume":"27","author":"Y Xu","year":"2020","unstructured":"Xu Y, Mu Y, Wang L, Zhang X (2020) Detailed analysis of molecular mechanisms in primary and metastatic melanoma. J Comput Biol 27:9\u201319. https:\/\/doi.org\/10.1089\/cmb.2019.0197","journal-title":"J Comput Biol"},{"key":"4219_CR30","doi-asserted-by":"publisher","first-page":"4909","DOI":"10.1158\/0008-5472.CAN-12-2194","volume":"72","author":"W Cruz-Mu\u00f1oz","year":"2012","unstructured":"Cruz-Mu\u00f1oz W, Jaramillo ML, Man S et al (2012) Roles for endothelin receptor B and BCL2A1 in spontaneous CNS metastasis of melanoma. Cancer Res 72:4909\u20134919. https:\/\/doi.org\/10.1158\/0008-5472.CAN-12-2194","journal-title":"Cancer Res"},{"key":"4219_CR31","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/1476-4598-9-69","volume":"9","author":"RF Kefford","year":"2010","unstructured":"Kefford RF, Clingan PR, Brady B et al (2010) A randomized, double-blind, placebo-controlled study of high-dose bosentan in patients with stage IV metastatic melanoma receiving first-line dacarbazine chemotherapy. Mol Cancer 9:69. https:\/\/doi.org\/10.1186\/1476-4598-9-69","journal-title":"Mol Cancer"},{"key":"4219_CR32","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-021-04089-x","volume":"79","author":"Y Duan","year":"2021","unstructured":"Duan Y, Chen R, Huang Y et al (2021) Tuning the ignition of CAR: optimizing the affinity of scFv to improve CAR-T therapy. Cell Mol Life Sci 79:14. https:\/\/doi.org\/10.1007\/s00018-021-04089-x","journal-title":"Cell Mol Life Sci"},{"key":"4219_CR33","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1007\/s10637-019-00832-1","volume":"38","author":"S Sandhu","year":"2020","unstructured":"Sandhu S, McNeil CM, LoRusso P et al (2020) Phase I study of the anti-endothelin B receptor antibody-drug conjugate DEDN6526A in patients with metastatic or unresectable cutaneous, mucosal, or uveal melanoma. Invest New Drugs 38:844\u2013854. https:\/\/doi.org\/10.1007\/s10637-019-00832-1","journal-title":"Invest New Drugs"},{"key":"4219_CR34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s44276-024-00109-y","volume":"3","author":"A Herbet","year":"2025","unstructured":"Herbet A, Hauti\u00e8re M, Jean-Alphonse F et al (2025) Targeting the activated allosteric conformation of the endothelin receptor B in melanoma with an antibody-drug conjugate: mechanisms and therapeutic efficacy. BJC Rep 3:1\u201311. https:\/\/doi.org\/10.1038\/s44276-024-00109-y","journal-title":"BJC Rep"},{"key":"4219_CR35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01066","author":"E Uribe-Querol","year":"2020","unstructured":"Uribe-Querol E, Rosales C (2020) Phagocytosis: our current understanding of a universal biological process. Front Immunol. https:\/\/doi.org\/10.3389\/fimmu.2020.01066","journal-title":"Front Immunol"},{"key":"4219_CR36","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/j.immuni.2016.04.020","volume":"44","author":"JH Esensten","year":"2016","unstructured":"Esensten JH, Helou YA, Chopra G et al (2016) CD28 costimulation: from mechanism to therapy. Immunity 44:973\u2013988. https:\/\/doi.org\/10.1016\/j.immuni.2016.04.020","journal-title":"Immunity"},{"key":"4219_CR37","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a021857","volume":"6","author":"ER Stanley","year":"2014","unstructured":"Stanley ER, Chitu V (2014) Csf-1 receptor signaling in myeloid cells. Cold Spring Harb Perspect Biol 6:a021857. https:\/\/doi.org\/10.1101\/cshperspect.a021857","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"4219_CR38","doi-asserted-by":"publisher","first-page":"1134661","DOI":"10.3389\/fimmu.2023.1134661","volume":"14","author":"M Mussbacher","year":"2023","unstructured":"Mussbacher M, Derler M, Bas\u00edlio J, Schmid JA (2023) NF-\u03baB in monocytes and macrophages \u2013 an inflammatory master regulator in multitalented immune cells. Front Immunol 14:1134661. https:\/\/doi.org\/10.3389\/fimmu.2023.1134661","journal-title":"Front Immunol"},{"key":"4219_CR39","doi-asserted-by":"publisher","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","volume":"2","author":"T Liu","year":"2017","unstructured":"Liu T, Zhang L, Joo D, Sun S-C (2017) NF-\u03baB signaling in inflammation. Sig Transduct Target Ther 2:17023. https:\/\/doi.org\/10.1038\/sigtrans.2017.23","journal-title":"Sig Transduct Target Ther"},{"key":"4219_CR40","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1189\/jlb.1A0414-212R","volume":"96","author":"A Busca","year":"2014","unstructured":"Busca A, Saxena M, Iqbal S et al (2014) PI3K\/Akt regulates survival during differentiation of human macrophages by maintaining NF-\u03baB-dependent expression of antiapoptotic Bcl-xL. J Leukoc Biol 96:1011\u20131022. https:\/\/doi.org\/10.1189\/jlb.1A0414-212R","journal-title":"J Leukoc Biol"},{"key":"4219_CR41","unstructured":"ENB Therapeutics Presents Top-line Results from Phase 1b ENBOLDEN-101 Study in Solid Tumors Refractory to Standard of Care at the Immuno-oncology Summit 2023, ENB Therapeutics."},{"key":"4219_CR42","doi-asserted-by":"crossref","unstructured":"Pineau D, Garcia L, Arnold H, et al 2025 Endothelin Signaling via EDNRB receptor Reduces Proliferation and Promotes Proneural-to-Mesenchymal Transition in Gliomas 05.674570 2025 09.","DOI":"10.1101\/2025.09.05.674570"},{"key":"4219_CR43","doi-asserted-by":"publisher","first-page":"3692","DOI":"10.3390\/cells11223692","volume":"11","author":"M Liu","year":"2022","unstructured":"Liu M, Liu J, Liang Z et al (2022) CAR-macrophages and CAR-T cells synergistically kill tumor cells in vitro. Cells 11:3692. https:\/\/doi.org\/10.3390\/cells11223692","journal-title":"Cells"}],"container-title":["Cancer Immunology, Immunotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-025-04219-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00262-025-04219-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-025-04219-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T14:45:37Z","timestamp":1764600337000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00262-025-04219-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,12]]},"references-count":43,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4219"],"URL":"https:\/\/doi.org\/10.1007\/s00262-025-04219-5","relation":{},"ISSN":["1432-0851"],"issn-type":[{"value":"1432-0851","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,12]]},"assertion":[{"value":"11 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 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":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"366"}}