{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T19:46:34Z","timestamp":1791747994018,"version":"4.3.4"},"reference-count":43,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"unspecified","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bavarian Cancer Research Centre","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/501100005972","name":"German Cancer Aid","doi-asserted-by":"crossref","award":["70114547"],"award-info":[{"award-number":["70114547"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008594","name":"European Hematology Association","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100008594","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["324392634 \u2013 TRR 221"],"award-info":[{"award-number":["324392634 \u2013 TRR 221"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["360372040 \u2013 SFB 1335"],"award-info":[{"award-number":["360372040 \u2013 SFB 1335"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["395357507 \u2013 SFB 1371"],"award-info":[{"award-number":["395357507 \u2013 SFB 1371"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["452409123"],"award-info":[{"award-number":["452409123"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["537477296"],"award-info":[{"award-number":["537477296"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005190","name":"Melanoma Research Alliance","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100005190","id-type":"DOI","asserted-by":"publisher"}]},{"name":"German Jos\u00e9 Carreras Foundation","award":["DJCLS 07 R\/2020"],"award-info":[{"award-number":["DJCLS 07 R\/2020"]}]},{"DOI":"10.13039\/100008672","name":"Wilhelm Sander Foundation","doi-asserted-by":"crossref","award":["2021.040.1"],"award-info":[{"award-number":["2021.040.1"]}],"id":[{"id":"10.13039\/100008672","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008672","name":"Wilhelm Sander Foundation","doi-asserted-by":"crossref","award":["2021.041.1"],"award-info":[{"award-number":["2021.041.1"]}],"id":[{"id":"10.13039\/100008672","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008672","name":"Wilhelm Sander Foundation","doi-asserted-by":"crossref","award":["2023.101.1"],"award-info":[{"award-number":["2023.101.1"]}],"id":[{"id":"10.13039\/100008672","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,4,3]]},"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Immune checkpoint inhibitors (ICIs) of programmed cell death protein-1 (PD-1) or cytotoxic T-lymphocytes-associated protein 4 (CTLA-4) reinvigorate strong polyclonal T-cell immune responses against tumor cells. For many patients, these therapies fail because the development of spontaneous immune responses is often compromised, as the tumor microenvironment (TME) lacks proinflammatory signals resulting in suboptimal activation of antigen-presenting cells (APCs). Necroptosis is a special form of programmed cell death associated with leakage of inflammatory factors that can lead to APC maturation. However, it is unclear to which extent functional necroptosis in tumor cells contributes to ICI immunotherapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>With genetically engineered tumor cell lines that lack specific components of the necroptosis machinery (mixed lineage kinase domain-like pseudokinase (MLKL), receptor interacting protein kinase 3 (RIPK3)), we addressed the importance of necroptotic tumor cell death for the efficacy of ICI immunotherapy in murine models. Preclinical data were aligned with genome-wide transcriptional programs in patient tumor samples at diagnosis and during ICI treatment for the activity of these pathways and association with treatment outcome.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Mice bearing MLKL-deficient or RIPK3-deficient tumors failed to control tumor growth in response to anti-PD-1\/anti-CTLA-4 immunotherapy. Mechanistically, defects in the necroptosis pathway resulted in reduced tumor antigen cross-presentation by type 1 conventional dendritic cells (DCs) in tumor-draining lymph nodes, and subsequently impaired immunotherapy-induced expansion of circulating tumor antigen-specific CD8<jats:sup>+<\/jats:sup> T cells and their accumulation and activation in the TME. In vitro, co-culture of tumor cells undergoing necroptotic but not apoptotic programmed cell death resulted in increased uptake by phagocytic cells, associated with maturation and activation of DCs. Treatment of tumors with the epigenetic modulator azacytidine enhanced intrinsic transcriptional activity of the necroptosis machinery, and hence their susceptibility to ICI immunotherapy. In humans, transcriptome analysis of melanoma samples revealed a strong association between high expression of <jats:italic>MLKL<\/jats:italic> and prolonged overall survival and durable clinical response to immunotherapy with anti-PD-1 and\/or anti-CTLA-4 checkpoint inhibitors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Defective necroptosis signaling in tumor cells is a cancer resistance mechanism to ICI immunotherapy. Reversion of epigenetic silencing of the necroptosis pathway can render tumors susceptible to checkpoint inhibition.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2024-010433","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T01:55:18Z","timestamp":1746755718000},"page":"e010433","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Defects in the necroptosis machinery are a cancer resistance mechanism to checkpoint inhibitor immunotherapy"],"prefix":"10.1136","volume":"13","author":[{"given":"Anna","family":"Sax","sequence":"first","affiliation":[{"name":"Department of Medicine III, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"},{"name":"Center for Translational Cancer Research (TranslaTUM), Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"May","sequence":"additional","affiliation":[{"name":"Department of Medicine III, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"},{"name":"Center for Translational Cancer Research (TranslaTUM), Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Enssle","sequence":"additional","affiliation":[{"name":"Department of Medicine III, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"},{"name":"Center for Translational Cancer Research (TranslaTUM), Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nardine","family":"Soliman","sequence":"additional","affiliation":[{"name":"Department of Medicine III, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"},{"name":"Center for Translational Cancer Research (TranslaTUM), Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Nedelko","sequence":"additional","affiliation":[{"name":"Department of Medicine III, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"},{"name":"Center for Translational Cancer Research (TranslaTUM), Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Mandracci","sequence":"additional","affiliation":[{"name":"Department of Medicine III, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"},{"name":"Center for Translational Cancer Research (TranslaTUM), Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"St\u00f6gbauer","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Joachim","sequence":"additional","affiliation":[{"name":"Department of Medicine III, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"},{"name":"Center for Translational Cancer Research (TranslaTUM), Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof","family":"Winter","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Pathobiochemistry, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"},{"name":"German Cancer Consortium (DKTK), Partner-site Munich and German Cancer Research Center (DKFZ), Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Bassermann","sequence":"additional","affiliation":[{"name":"Department of Medicine III, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"},{"name":"Center for Translational Cancer Research (TranslaTUM), Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"},{"name":"German Cancer Consortium (DKTK), Partner-site Munich and German Cancer Research Center (DKFZ), Heidelberg, Germany"},{"name":"Bavarian Cancer Research Center (BZKF), Munich & Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Steiger","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"El Khawanky","sequence":"additional","affiliation":[{"name":"Department of Medicine III, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"},{"name":"Center for Translational Cancer Research (TranslaTUM), Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Poeck","sequence":"additional","affiliation":[{"name":"Bavarian Cancer Research Center (BZKF), Munich & Regensburg, Germany"},{"name":"Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany"},{"name":"Leibniz Institute for Immunotherapy (LIT), Regensburg, Germany"},{"name":"Center for immunomedicine in transplantation and oncology (CITO), Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6394-5130","authenticated-orcid":false,"given":"Simon","family":"Heidegger","sequence":"additional","affiliation":[{"name":"Department of Medicine III, Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"},{"name":"Center for Translational Cancer Research (TranslaTUM), Technical University of Munich, TUM School of Medicine and Health, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"key":"2025100311552280000_13.5.e010433.1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3845"},{"key":"2025100311552280000_13.5.e010433.2","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.107"},{"key":"2025100311552280000_13.5.e010433.3","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/s41568-024-00674-x","article-title":"Immunogenic cell death in cancer: targeting necroptosis to induce antitumour immunity","volume":"24","author":"Meier","year":"2024","journal-title":"Nat Rev Cancer"},{"key":"2025100311552280000_13.5.e010433.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05691-6"},{"key":"2025100311552280000_13.5.e010433.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-019-0164-5"},{"key":"2025100311552280000_13.5.e010433.6","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-021-23004-3","article-title":"ZBP1 not RIPK1 mediates tumor necroptosis in breast cancer","volume":"12","author":"Baik","year":"2021","journal-title":"Nat Commun"},{"key":"2025100311552280000_13.5.e010433.7","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1038\/s41418-021-00785-0","article-title":"MLKL in cancer: more than a necroptosis regulator","volume":"28","author":"Martens","year":"2021","journal-title":"Cell Death Differ"},{"key":"2025100311552280000_13.5.e010433.8","doi-asserted-by":"crossref","DOI":"10.1016\/j.xpro.2022.101457","article-title":"Examining MLKL phosphorylation to detect necroptosis in murine mammary tumors","volume":"3","author":"Baik","year":"2022","journal-title":"STAR Protoc"},{"key":"2025100311552280000_13.5.e010433.9","doi-asserted-by":"publisher","DOI":"10.1016\/J.CCELL.2019.01.003"},{"key":"2025100311552280000_13.5.e010433.10","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.2004088","article-title":"Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal","volume":"6","author":"Gao","year":"2013","journal-title":"Sci Signal"},{"key":"2025100311552280000_13.5.e010433.11","unstructured":"Jacobsen A . cgdsr: R-Based API for Accessing the MSKCC Cancer Genomics Data Server (CGDS). R package version 1.3.0. 2018 Available: https:\/\/github.com\/cBioPortal\/cgdsr"},{"key":"2025100311552280000_13.5.e010433.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2023.10.053"},{"key":"2025100311552280000_13.5.e010433.13","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2018.1462431","article-title":"TumGrowth: An open-access web tool for the statistical analysis of tumor growth curves","volume":"7","author":"Enot","year":"2018","journal-title":"Oncoimmunology"},{"key":"2025100311552280000_13.5.e010433.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.06.001"},{"key":"2025100311552280000_13.5.e010433.15","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.trecan.2018.09.001","article-title":"The Role of Type 1 Conventional Dendritic Cells in Cancer Immunity","volume":"4","author":"B\u00f6ttcher","year":"2018","journal-title":"Trends Cancer"},{"key":"2025100311552280000_13.5.e010433.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.01.004"},{"key":"2025100311552280000_13.5.e010433.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.04.003"},{"key":"2025100311552280000_13.5.e010433.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.04.010"},{"key":"2025100311552280000_13.5.e010433.19","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2015.56"},{"key":"2025100311552280000_13.5.e010433.20","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-3683"},{"key":"2025100311552280000_13.5.e010433.21","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-018-05979-8","article-title":"Treatment with mRNA coding for the necroptosis mediator MLKL induces antitumor immunity directed against neo-epitopes","volume":"9","author":"Van Hoecke","year":"2018","journal-title":"Nat Commun"},{"key":"2025100311552280000_13.5.e010433.22","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.aaw2004","article-title":"Intratumoral activation of the necroptotic pathway components RIPK1 and RIPK3 potentiates antitumor immunity","volume":"4","author":"Snyder","year":"2019","journal-title":"Sci Immunol"},{"key":"2025100311552280000_13.5.e010433.23","doi-asserted-by":"crossref","DOI":"10.3390\/cells9081823","article-title":"Necroptosis in Immuno-Oncology and Cancer Immunotherapy","volume":"9","author":"Sprooten","year":"2020","journal-title":"Cells"},{"key":"2025100311552280000_13.5.e010433.24","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.aau8943","article-title":"RIG-I activation is critical for responsiveness to checkpoint blockade","volume":"4","author":"Heidegger","year":"2019","journal-title":"Sci Immunol"},{"key":"2025100311552280000_13.5.e010433.25","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8420"},{"key":"2025100311552280000_13.5.e010433.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.09.065"},{"key":"2025100311552280000_13.5.e010433.27","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701492"},{"key":"2025100311552280000_13.5.e010433.28","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/s41586-022-04753-7","article-title":"ADAR1 masks the cancer immunotherapeutic promise of ZBP1-driven necroptosis","volume":"606","author":"Zhang","year":"2022","journal-title":"Nature New Biol"},{"key":"2025100311552280000_13.5.e010433.29","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2016.1149673","article-title":"Contribution of RIP3 and MLKL to immunogenic cell death signaling in cancer chemotherapy","volume":"5","author":"Yang","year":"2016","journal-title":"Oncoimmunology"},{"key":"2025100311552280000_13.5.e010433.30","doi-asserted-by":"crossref","unstructured":"Yang Y , Wu M , Cao D , et al . ZBP1-MLKL necroptotic signaling potentiates radiation-induced antitumor immunity via intratumoral STING pathway activation. Sci Adv 2021;7. doi:10.1126\/sciadv.abf6290","DOI":"10.1126\/sciadv.abf6290"},{"key":"2025100311552280000_13.5.e010433.31","doi-asserted-by":"crossref","first-page":"E31","DOI":"10.25011\/cim.v42i1.32390","article-title":"RIPK3 expression as a potential predictive and prognostic marker in metastatic colon cancer","volume":"42","author":"Conev","year":"2019","journal-title":"Clin Invest Med"},{"key":"2025100311552280000_13.5.e010433.32","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1177\/1533034616655909","article-title":"Association of Mixed Lineage Kinase Domain-Like Protein Expression With Prognosis in Patients With Colon Cancer","volume":"16","author":"Li","year":"2017","journal-title":"Technol Cancer Res Treat"},{"key":"2025100311552280000_13.5.e010433.33","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.2005756","article-title":"BRAF and AXL oncogenes drive RIPK3 expression loss in cancer","volume":"16","author":"Najafov","year":"2018","journal-title":"PLoS Biol"},{"key":"2025100311552280000_13.5.e010433.34","doi-asserted-by":"crossref","first-page":"5034","DOI":"10.18632\/aging.204124","article-title":"Multi-omics analysis reveals the panoramic picture of necroptosis-related regulators in pan-cancer","volume":"14","author":"Li","year":"2022","journal-title":"Aging (Milano)"},{"key":"2025100311552280000_13.5.e010433.35","doi-asserted-by":"crossref","DOI":"10.1186\/s12885-018-4655-4","article-title":"Prognostic and clinicopathological significance of MLKL expression in cancer patients: a meta-analysis","volume":"18","author":"Hu","year":"2018","journal-title":"BMC Cancer"},{"key":"2025100311552280000_13.5.e010433.36","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-018-0058-y"},{"key":"2025100311552280000_13.5.e010433.37","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/s41419-020-2538-5","article-title":"Necroptosis in head and neck squamous cell carcinoma: characterization of clinicopathological relevance and in vitro cell model","volume":"11","author":"Li","year":"2020","journal-title":"Cell Death Dis"},{"key":"2025100311552280000_13.5.e010433.38","doi-asserted-by":"publisher","DOI":"10.1172\/JCI87545"},{"key":"2025100311552280000_13.5.e010433.39","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2071-9"},{"key":"2025100311552280000_13.5.e010433.40","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41586-020-2079-1","article-title":"A bioorthogonal system reveals antitumour immune function of pyroptosis","volume":"579","author":"Wang","year":"2020","journal-title":"Nature New Biol"},{"key":"2025100311552280000_13.5.e010433.41","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms14128","article-title":"Cleavage of DFNA5 by caspase-3 during apoptosis mediates progression to secondary necrotic\/pyroptotic cell death","volume":"8","author":"Rogers","year":"2017","journal-title":"Nat Commun"},{"key":"2025100311552280000_13.5.e010433.42","doi-asserted-by":"crossref","first-page":"847345","DOI":"10.3389\/fimmu.2022.847345","article-title":"Programmed Cell Death Tunes Tumor Immunity","volume":"13","author":"Liu","year":"2022","journal-title":"Front Immunol"},{"key":"2025100311552280000_13.5.e010433.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109858"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2024-010433","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T18:55:33Z","timestamp":1759517733000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2024-010433"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5]]},"references-count":43,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5,8]]},"published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1136\/jitc-2024-010433"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2024-010433","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5]]}}}