{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T04:14:28Z","timestamp":1788322468214,"version":"build-2803163510"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Advanced metastatic colorectal cancer (CRC) with deficient DNA mismatch repair (MMR-d), or immune-hot CRCs, show significantly improved clinical outcomes compared to MMR-proficient (MMR-p), or immune-cold CRCs. While the prior represents about 5% of all CRCs, the latter represent 95% and are characterized by low immunogenicity. This study investigates bis-diethyldithiocarbamate (CuET), a novel anticancer compound, and its impact on the colorectal cancer tumor microenvironment (TME). CuET is shown to convert immunologically inactive tumors into hotbeds of antitumor immune responses, marked by increased lymphocyte infiltration, heightened cytotoxicity of natural killer (NK) and T cells, and enhanced non-self recognition by lymphocytes. The potent anticancer cytotoxicity and\n                    <jats:italic>in vivo<\/jats:italic>\n                    safety and efficacy of CuET are established. In summary, CuET transforms the colorectal cancer TME, bolstering NK and T cell cytotoxicity and refining tumor cell recognition through non-classical activation via the NKG2D\/NKG2DL axis. This study unveils a novel mechanism of action for CuET: a potent immunomodulator capable of turning cold tumors hot.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1491450","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T02:25:52Z","timestamp":1739327152000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Diethyldithiocarbamate-copper complex ignites the tumor microenvironment through NKG2D-NKG2DL axis"],"prefix":"10.3389","volume":"16","author":[{"given":"Daciana C.","family":"Dumut","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"Hajduch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda M.","family":"Zacharias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingling","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo","family":"Frydrych","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Rozankova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miroslav","family":"Popper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dusan","family":"Garic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radu Alexandru","family":"Paun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Centorame","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhi","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Mistrik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Dzubak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan B.","family":"De Sanctis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danuta","family":"Radzioch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21772","article-title":"Colorectal cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA: A Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32319-0","article-title":"Colorectal cancer","volume":"394","author":"Dekker","year":"2019","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1500596","article-title":"PD-1 blockade in tumors with mismatch-repair deficiency","volume":"372","author":"Le","year":"2015","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-2176","article-title":"Facts and hopes in colorectal cancer immunotherapy","volume":"29","author":"Foote","year":"2023","journal-title":"Clin Cancer Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1126\/science.1129139","article-title":"Type, density, and location of immune cells within human colorectal tumors predict clinical outcome","volume":"313","author":"Galon","year":"2006","journal-title":"Science"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nature13954","article-title":"PD-1 blockade induces responses by inhibiting adaptive immune resistance","volume":"515","author":"Tumeh","year":"2014","journal-title":"Nature"},{"key":"B7","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1126\/science.aaa4971","article-title":"Neoantigens in cancer immunotherapy","volume":"348","author":"Schumacher","year":"2015","journal-title":"Science"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e1226","DOI":"10.1002\/cti2.v9.12","article-title":"Therapeutic strategies to remodel immunologically cold tumors","volume":"9","author":"Wang","year":"2020","journal-title":"Clin Transl Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(91)90446-C","article-title":"Disulfiram metabolism as a requirement for the inhibition of rat liver mitochondrial low Km aldehyde dehydrogenase","volume":"42","author":"Yourick","year":"1991","journal-title":"Biochem Pharmacol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1186\/s13643-021-01858-4","article-title":"Anticancer effects of disulfiram: a systematic review of in vitro, animal, and human studies","volume":"11","author":"Wang","year":"2022","journal-title":"Systematic Rev"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.752825","article-title":"The disulfiram\/copper complex induces autophagic cell death in colorectal cancer by targeting ULK1","volume":"12","author":"Hu","year":"2021","journal-title":"Front Pharmacol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2022.10.027","article-title":"Disulfiram-loaded hollow copper sulfide nanoparticles show anti-tumor effects in preclinical models of colorectal cancer","volume":"635","author":"Jiapaer","year":"2022","journal-title":"Biochem Biophys Res Commun"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics11110610","article-title":"Development of injectable PEGylated liposome encapsulating disulfiram for colorectal cancer treatment","volume":"11","author":"Najlah","year":"2019","journal-title":"Pharmaceutics"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2217\/nnm-2024-0007","article-title":"Synergistic eradicating impact of 5-fluouracil with FeO nanoparticles-diethyldithiocarbamate in colon cancer spheroids","volume":"19","author":"Abu-Serie","year":"2024","journal-title":"Nanomedicine (Lond)"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.2174\/1574892812666170424144925","article-title":"In vitro collapsing colon cancer cells by selectivity of disulfiram-loaded charge switchable nanoparticles against cancer stem cells","volume":"12","author":"Abu-Serie","year":"2017","journal-title":"Recent Pat Anticancer Drug Discovery"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-1035","article-title":"High-throughput cell-based screening of 4910 known drugs and drug-like small molecules identifies disulfiram as an inhibitor of prostate cancer cell growth","volume":"15","author":"Iljin","year":"2009","journal-title":"Clin Cancer Res"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-2126","article-title":"Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cultures and xenografts via inhibition of the proteasome activity","volume":"66","author":"Chen","year":"2006","journal-title":"Cancer Res"},{"key":"B18","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1186\/1479-5876-12-163","article-title":"Disulfiram targeting lymphoid Malignant cell lines via ROS-JNK activation as well as Nrf2 and NF-kB pathway inhibition","volume":"12","author":"Zha","year":"2014","journal-title":"J Transl Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2021.741316","article-title":"Recent advances in repurposing disulfiram and disulfiram derivatives as copper-dependent anticancer agents","volume":"8","author":"Kannappan","year":"2021","journal-title":"Front Mol Biosci"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2015.02.007","article-title":"Disulfiram (DSF) acts as a copper ionophore to induce copper-dependent oxidative stress and mediate anti-tumor efficacy in inflammatory breast cancer","volume":"9","author":"Allensworth","year":"2015","journal-title":"Mol Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/nature25016","article-title":"Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4","volume":"552","author":"Skrott","year":"2017","journal-title":"Nature"},{"key":"B22","doi-asserted-by":"publisher","first-page":"300060520925996","DOI":"10.1177\/0300060520925996","article-title":"The anti-alcohol dependency drug disulfiram inhibits the viability and progression of gastric cancer cells by regulating the Wnt and NF-\u03baB pathways","volume":"48","author":"Zhang","year":"2020","journal-title":"J Int Med Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2022.2038434","article-title":"Disulfiram\/Copper induces antitumor activity against gastric cancer via the ROS\/MAPK and NPL4 pathways","volume":"13","author":"Liu","year":"2022","journal-title":"Bioengineered"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.2174\/138955712802762068","article-title":"Diethyldithiocarbamate complex with copper: the mechanism of action in cancer cells","volume":"12","author":"Skrott","year":"2012","journal-title":"Mini Rev Med Chem"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12010138","article-title":"Disulfiram\/Copper Induces Antitumor Activity against Both Nasopharyngeal Cancer Cells and Cancer-Associated Fibroblasts through ROS\/MAPK and Ferroptosis Pathways","volume":"12","author":"Li","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.18632\/oncoscience.v1i1","article-title":"Disulfiram\/copper causes redox-related proteotoxicity and concomitant heat shock response in ovarian cancer cells that is augmented by auranofin-mediated thioredoxin inhibition","volume":"1","author":"Papaioannou","year":"2014","journal-title":"Oncoscience"},{"key":"B27","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1093\/carcin\/bgt366","article-title":"Disulfiram is a direct and potent inhibitor of human O6-methylguanine-DNA methyltransferase (MGMT) in brain tumor cells and mouse brain and markedly increases the alkylating DNA damage","volume":"35","author":"Paranjpe","year":"2014","journal-title":"Carcinogenesis"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s10517-022-05447-w","article-title":"Anti-cancer effects of disulfiram in cervical cancer cell lines are mediated by both autophagy and apoptosis","volume":"172","author":"Zhang","year":"2022","journal-title":"Bull Exp Biol Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s43440-020-00122-1","article-title":"Disulfiram potentiates docetaxel cytotoxicity in breast cancer cells through enhanced ROS and autophagy","volume":"72","author":"Swetha","year":"2020","journal-title":"Pharmacol Rep"},{"key":"B30","article-title":"Induction of autophagy-dependent apoptosis in cancer cells through activation of ER stress: an uncovered anti-cancer mechanism by anti-alcoholism drug disulfiram","volume":"9","author":"Zhang","year":"2019","journal-title":"Am J Cancer Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13194852","article-title":"At the cutting edge against cancer: A perspective on immunoproteasome and immune checkpoints modulation as a potential therapeutic intervention","volume":"13","author":"Tundo","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.734853","article-title":"Disulfiram improves the anti-PD-1 therapy efficacy by regulating PD-L1 expression via epigenetically reactivation of IRF7 in triple negative breast cancer","volume":"11","author":"Zheng","year":"2021","journal-title":"Front Oncol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e110636","DOI":"10.15252\/embj.2022110636","article-title":"Disulfiram bolsters T-cell anti-tumor immunity through direct activation of LCK-mediated TCR signaling","volume":"41","author":"Wang","year":"2022","journal-title":"EMBO J"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-0471","article-title":"Intratumoral copper modulates PD-L1 expression and influences tumor immune evasion","volume":"80","author":"Voli","year":"2020","journal-title":"Cancer Res"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00097","article-title":"NKG2D ligands in tumor immunity: two sides of a coin","volume":"6","author":"Zhang","year":"2015","journal-title":"Front Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00476","article-title":"NKG2D and its ligands: \"One for all, all for one","volume":"9","author":"Zingoni","year":"2018","journal-title":"Front Immunol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s12943-019-0956-8","article-title":"Natural killer group 2D receptor and its ligands in cancer immune escape","volume":"18","author":"Duan","year":"2019","journal-title":"Mol Cancer"},{"key":"B38","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.coi.2018.02.004","article-title":"NKG2D and its ligands in cancer","volume":"51","author":"Dhar","year":"2018","journal-title":"Curr Opin Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.713158","article-title":"Leveraging NKG2D ligands in immuno-oncology","volume":"12","author":"Fuertes","year":"2021","journal-title":"Front Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.24568","article-title":"Novel therapeutic features of disulfiram against hepatocellular carcinoma cells with inhibitory effects on a disintegrin and metalloproteinase 10","volume":"9","author":"Goto","year":"2018","journal-title":"Oncotarget"},{"key":"B41","article-title":"Establishment of mouse colonic carcinoma cell lines with different metastatic properties","volume":"40","author":"Brattain","year":"1980","journal-title":"Cancer Res"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.179","article-title":"Sulforhodamine B colorimetric assay for cytotoxicity screening","volume":"1","author":"Vichai","year":"2006","journal-title":"Nat Protoc"},{"key":"B43","doi-asserted-by":"publisher","first-page":"100262","DOI":"10.1016\/j.xpro.2020.100262","article-title":"Flow cytometry-based ex vivo murine NK cell cytotoxicity assay","volume":"2","author":"Wong","year":"2021","journal-title":"STAR Protoc"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.01.004","article-title":"Cytotoxic T lymphocytes efficiently recognize human colon cancer stem-like cells","volume":"178","author":"Inoda","year":"2011","journal-title":"Am J Pathol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1111\/j.1600-065X.1977.tb00242.x","article-title":"Cellular requirements for the induction of cytotoxic T cells","volume":"35","author":"Davidson","year":"1977","journal-title":"vitro. Immunol Rev"},{"key":"B46","doi-asserted-by":"publisher","first-page":"100961","DOI":"10.1016\/j.xpro.2021.100961","article-title":"Isolation and enrichment of mouse splenic T cells for ex vivo and in vivo T cell receptor stimulation assays","volume":"2","author":"Grosjean","year":"2021","journal-title":"STAR Protoc"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1002\/jso.v126.5","article-title":"Colorectal cancer","volume":"126","author":"Paty","year":"2022","journal-title":"J Surg Oncol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.ctrv.2019.04.003","article-title":"Immunotherapy of colorectal cancer: Challenges for therapeutic efficacy","volume":"76","author":"Ciardiello","year":"2019","journal-title":"Cancer Treat Rev"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00369","article-title":"Relationships between immune landscapes, genetic subtypes and responses to immunotherapy in colorectal cancer","volume":"11","author":"Picard","year":"2020","journal-title":"Front Immunol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/nrc3245","article-title":"The immune contexture in human tumours: impact on clinical outcome","volume":"12","author":"Fridman","year":"2012","journal-title":"Nat Rev Cancer"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3175","article-title":"A colorectal cancer classification system that associates cellular phenotype and responses to therapy","volume":"19","author":"Sadanandam","year":"2013","journal-title":"Nat Med"},{"key":"B52","article-title":"Tumor-infiltrating lymphocytes in colorectal cancer: the fundamental indication and application on immunotherapy","volume":"12","author":"Bai","year":"2021","journal-title":"Front Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-2907","article-title":"Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer","volume":"71","author":"Tosolini","year":"2011","journal-title":"Cancer Res"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2022.04.010","article-title":"Turning cold tumors hot: from molecular mechanisms to clinical applications","volume":"43","author":"Zhang","year":"2022","journal-title":"Trends Immunol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-023-00600-4","article-title":"CD8+ T cells maintain killing of MHC-I-negative tumor cells through the NKG2D\u2013NKG2DL axis","volume":"4","author":"Lerner","year":"2023","journal-title":"Nat Cancer"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2017.161","article-title":"Functions of NKG2D in CD8(+) T cells: an opportunity for immunotherapy","volume":"15","author":"Prajapati","year":"2018","journal-title":"Cell Mol Immunol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-019-02343-7","article-title":"Characterization of circulating T-, NK-, and NKT cell subsets in patients with colorectal cancer: the peripheral blood immune cell profile","volume":"68","author":"Krijgsman","year":"2019","journal-title":"Cancer Immunology Immunotherapy"},{"key":"B58","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/1471-2407-12-24","article-title":"NKG2D ligand tumor expression and association with clinical outcome in early breast cancer patients: an observational study","volume":"12","author":"de Kruijf","year":"2012","journal-title":"BMC Cancer"},{"key":"B59","doi-asserted-by":"publisher","first-page":"6993","DOI":"10.1158\/1078-0432.CCR-09-0991","article-title":"NKG2D ligand expression in human colorectal cancer reveals associations with prognosis and evidence for immunoediting","volume":"15","author":"McGilvray","year":"2009","journal-title":"Clin Cancer Res"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00095-4","article-title":"ULBPs, novel MHC class I\u2013related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor","volume":"14","author":"Cosman","year":"2001","journal-title":"Immunity"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-2973","article-title":"amp]]amp; Reyburn, H.T. Selective induction of expression of a ligand for the NKG2D receptor by proteasome inhibitors","volume":"68","author":"Vale\u0301s-Go\u0301mez","year":"2008","journal-title":"Cancer Res"},{"key":"B62","article-title":"Role of NKG2D and its ligands in cancer immunotherapy","volume":"9","author":"Liu","year":"2019","journal-title":"Am J Cancer Res"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.3390\/vaccines10071033","article-title":"NK cell-based immunotherapy in colorectal cancer","volume":"10","author":"Della Chiesa","year":"2022","journal-title":"Vaccines"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.03.011","article-title":"Adoptive transfer of NKG2D CAR mRNA-engineered natural killer cells in colorectal cancer patients","volume":"27","author":"Xiao","year":"2019","journal-title":"Mol Ther"},{"key":"B65","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1186\/s12943-019-1091-2","article-title":"Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4","volume":"18","author":"Qin","year":"2019","journal-title":"Mol Cancer"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11080749","article-title":"LAG-3 expression predicts outcome in stage II colon cancer","volume":"11","author":"Rhyner Agocs","year":"2021","journal-title":"J Pers Med"},{"key":"B67","doi-asserted-by":"publisher","first-page":"e1249561","DOI":"10.1080\/2162402X.2016.1249561","article-title":"Compensatory upregulation of PD-1, LAG-3, and CTLA-4 limits the efficacy of single-agent checkpoint blockade in metastatic ovarian cancer","volume":"6","author":"Huang","year":"2017","journal-title":"Oncoimmunology"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1491450\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T02:25:57Z","timestamp":1739327157000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1491450\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,12]]},"references-count":67,"alternative-id":["10.3389\/fimmu.2025.1491450"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1491450","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,12]]},"article-number":"1491450"}}