{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:38:41Z","timestamp":1792046321577,"version":"4.4.0"},"reference-count":140,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science & Technology Department Foundation of Jilin Province","award":["20230505034ZP"],"award-info":[{"award-number":["20230505034ZP"]}]},{"award":["20230505034ZP"],"award-info":[{"award-number":["20230505034ZP"]}],"id":[{"id":"https:\/\/ror.org\/049x38272","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Trained immunity refers to the enduring functional reprogramming of innate immune cells after particular stimuli, driven by epigenetic and metabolic alterations that augment non-specific responses upon subsequent exposure. Neutrophils and monocytes\/macrophages, as essential innate effectors, are crucial for the induction and control of trained immunity, which is the primary emphasis of this review. Neutrophils, the predominant circulating leukocytes, were historically considered incapable of memory owing to their brief lifespan. Emerging evidence indicates that trained immunity functions at the bone marrow progenitor level, influencing granulopoiesis to produce neutrophils with lasting functional modifications. This research offers new insights into neutrophil functions in infection, cancer, and inflammation. Monocytes and macrophages, characterized by phenotypic plasticity and tissue residence, function as conventional models of trained immunity. They experience direct peripheral reprogramming or emerge as primed descendants of trained bone marrow precursors, performing pro-inflammatory or reparative roles in malignancies, infections, and ischemia lesions. This study comprehensively outlines the regulatory mechanisms of trained immunity in these cells, clarifies their functions in various clinical situations, and examines therapeutic applications. Comprehending these pathways is crucial for elucidating the cellular foundation of innate immunological memory, uncovering its multiple functions in disease, and guiding innovative therapeutics aimed at granulopoiesis and monocyte-macrophage polarization.<\/jats:p>","DOI":"10.3390\/cells15090752","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T09:09:12Z","timestamp":1776935352000},"page":"752","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Trained Immunity in Neutrophils and Mononuclear Phagocytes: Mechanisms and Pathophysiological Functions"],"prefix":"10.3390","volume":"15","author":[{"given":"Wanying","family":"Li","sequence":"first","affiliation":[{"name":"College of Basic Medical Sciences, Key Laboratory of Pathobiology, Ministry of Education, Medical Basic Research Innovation Center of Airway Disease in North China, Jilin University, Changchun 130021, China"},{"name":"Department of Radiological Medicine, School of Public Health, Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3969-0481","authenticated-orcid":false,"given":"Jialei","family":"Wei","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Key Laboratory of Pathobiology, Ministry of Education, Medical Basic Research Innovation Center of Airway Disease in North China, Jilin University, Changchun 130021, China"},{"name":"Department of Radiological Medicine, School of Public Health, Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9198-9413","authenticated-orcid":false,"given":"Liyuan","family":"Li","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Key Laboratory of Pathobiology, Ministry of Education, Medical Basic Research Innovation Center of Airway Disease in North China, Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, Key Laboratory of Pathobiology, Ministry of Education, Medical Basic Research Innovation Center of Airway Disease in North China, Jilin University, Changchun 130021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1056\/NEJM200008033430506","article-title":"Innate immunity","volume":"343","author":"Medzhitov","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/s41577-020-0285-6","article-title":"Defining trained immunity and its role in health and disease","volume":"20","author":"Netea","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"aaf1098","DOI":"10.1126\/science.aaf1098","article-title":"Trained immunity: A program of innate immune memory in health and disease","volume":"352","author":"Netea","year":"2016","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"109930","DOI":"10.1016\/j.clim.2024.109930","article-title":"Trained immunity-inducing vaccines: Harnessing innate memory for vaccine design and delivery","volume":"261","author":"Baydemir","year":"2024","journal-title":"Clin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/s41573-019-0025-4","article-title":"Therapeutic targeting of trained immunity","volume":"18","author":"Mulder","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"102190","DOI":"10.1016\/j.coi.2022.102190","article-title":"Trained immunity: Implications for vaccination","volume":"77","author":"Geckin","year":"2022","journal-title":"Curr. Opin. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.it.2019.04.013","article-title":"The Neutrophil Life Cycle","volume":"40","author":"Hidalgo","year":"2019","journal-title":"Trends Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41577-019-0141-8","article-title":"Heterogeneity of neutrophils","volume":"19","author":"Ng","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1152\/physrev.00012.2018","article-title":"The Neutrophil\u2019s Role During Health and Disease","volume":"99","author":"Liew","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1172\/JCI108517","article-title":"Neutrophil kinetics in man","volume":"58","author":"Dancey","year":"1976","journal-title":"J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1182\/blood.V100.3.854","article-title":"Evaluation of role of G-CSF in the production, survival, and release of neutrophils from bone marrow into circulation","volume":"100","author":"Basu","year":"2002","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1182\/blood-2010-01-259028","article-title":"In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days","volume":"116","author":"Pillay","year":"2010","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/s12964-025-02192-1","article-title":"Hematopoietic stem cell state and fate in trained immunity","volume":"23","author":"Liao","year":"2025","journal-title":"Cell Commun. Signal."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1182\/blood-2012-05-431114","article-title":"Antibacterial effect of microvesicles released from human neutrophilic granulocytes","volume":"121","author":"Lorincz","year":"2013","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nrc.2016.52","article-title":"Neutrophils in cancer: Neutral no more","volume":"16","author":"Coffelt","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nri.2017.36","article-title":"The immunopathology of sepsis and potential therapeutic targets","volume":"17","author":"Scicluna","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7795","DOI":"10.2147\/JIR.S513325","article-title":"The Role of Pattern Recognition Receptors in Epigenetic and Metabolic Reprogramming: Insights into Trained Immunity","volume":"18","author":"Li","year":"2025","journal-title":"J. Inflamm. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1152\/physrev.00031.2021","article-title":"Trained immunity: Adaptation within innate immune mechanisms","volume":"103","author":"Bekkering","year":"2023","journal-title":"Physiol. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1182\/blood.V15.6.840.840","article-title":"Evaluation of marrow granulocytic reserves in normal and disease states","volume":"15","author":"Craddock","year":"1960","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1172\/JCI103750","article-title":"Quantitative measurement of the erythrocytic and granulocytic cells of the marrow and blood","volume":"37","author":"Donohue","year":"1958","journal-title":"J. Clin. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.tem.2018.03.012","article-title":"Altered Cellular Metabolism Drives Trained Immunity","volume":"29","author":"Sohrabi","year":"2018","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.clicom.2022.08.004","article-title":"Trained innate immunity and diseases: Bane with the boon","volume":"2","author":"Mishra","year":"2022","journal-title":"Clin. Immunol. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/s41588-018-0341-3","article-title":"Publisher Correction: Immune genes are primed for robust transcription by proximal long noncoding RNAs located in nuclear compartments","volume":"51","author":"Fanucchi","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1002\/jlb.66.6.889","article-title":"Macrophage responses to hypoxia: Relevance to disease mechanisms","volume":"66","author":"Lewis","year":"1999","journal-title":"J. Leukoc. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1126\/science.1178331","article-title":"Development of monocytes, macrophages, and dendritic cells","volume":"327","author":"Geissmann","year":"2010","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1146\/annurev.immunol.021908.132557","article-title":"Blood monocytes: Development, heterogeneity, and relationship with dendritic cells","volume":"27","author":"Auffray","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1038\/ni.2705","article-title":"Tissue-resident macrophages","volume":"14","author":"Davies","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/nri3671","article-title":"Monocytes and macrophages: Developmental pathways and tissue homeostasis","volume":"14","author":"Ginhoux","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.immuni.2013.08.007","article-title":"Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes","volume":"39","author":"Jakubzick","year":"2013","journal-title":"Immunity"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1016\/j.immuni.2012.08.026","article-title":"Ly6C hi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells","volume":"37","author":"Zigmond","year":"2012","journal-title":"Immunity"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.pt.2023.07.007","article-title":"Monocytes as primary defenders against Toxoplasma gondii infection","volume":"39","author":"Orchanian","year":"2023","journal-title":"Trends Parasitol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Savinetti, I., Papagna, A., and Foti, M. (2021). Human Monocytes Plasticity in Neurodegeneration. Biomedicines, 9.","DOI":"10.3390\/biomedicines9070717"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e658","DOI":"10.1002\/mco2.658","article-title":"Macrophage plasticity: Signaling pathways, tissue repair, and regeneration","volume":"5","author":"Yan","year":"2024","journal-title":"MedComm"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1172\/JCI59643","article-title":"Macrophage plasticity and polarization: In vivo veritas","volume":"122","author":"Sica","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1038\/s41598-024-51620-8","article-title":"Dectin-1 ligands produce distinct training phenotypes in human monocytes through differential activation of signaling networks","volume":"14","author":"Cheng","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Antunes, M., Sugiyama, F.H.C., Gravina, H.D., Castro, R.C., Mercado, F.J.R., de Lima, J.O., Fontanari, C., and Frantz, F.G. (2023). COVID-19 inactivated and non-replicating viral vector vaccines induce regulatory training phenotype in human monocytes under epigenetic control. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1200789"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1161\/CIRCRESAHA.117.312465","article-title":"Trained Innate Immunity as a Novel Mechanism Linking Infection and the Development of Atherosclerosis","volume":"122","author":"Leentjens","year":"2018","journal-title":"Circ. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"114324","DOI":"10.1016\/j.celrep.2024.114324","article-title":"Tissue-resident trained immunity in hepatocytes protects against septic liver injury in zebrafish","volume":"43","author":"Wang","year":"2024","journal-title":"Cell Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100897","DOI":"10.1016\/j.mam.2020.100897","article-title":"Immunometabolic control of trained immunity","volume":"77","author":"Riksen","year":"2021","journal-title":"Mol. Asp. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"105518","DOI":"10.1016\/j.jbc.2023.105518","article-title":"Mucosal recombinant BCG vaccine induces lung-resident memory macrophages and enhances trained immunity via mTORC2\/HK1-mediated metabolic rewiring","volume":"300","author":"Peng","year":"2024","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Hern\u00e1ndez, C.A., Kern, C.C., Butkeviciute, E., McCarthy, E., Dockrell, H.M., Moreno-Altamirano, M.M.B., Aguilar-L\u00f3pez, B.A., Bhosale, G., Wang, H., and Gems, D. (2020). Mitochondrial Signature in Human Monocytes and Resistance to Infection in C. elegans During Fumarate-Induced Innate Immune Training. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01715"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3968","DOI":"10.4049\/jimmunol.1600345","article-title":"Correction: Dectin-1 Activation by a Natural Product \u03b2-Glucan Converts Immunosuppressive Macrophages into an M1-like Phenotype","volume":"196","author":"Liu","year":"2016","journal-title":"J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s00395-022-00935-6","article-title":"Innate immune cells in the pathophysiology of calcific aortic valve disease: Lessons to be learned from atherosclerotic cardiovascular disease?","volume":"117","author":"Broeders","year":"2022","journal-title":"Basic Res. Cardiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"102956","DOI":"10.1016\/j.jaut.2022.102956","article-title":"Involvement of trained immunity during autoimmune responses","volume":"137","author":"Mora","year":"2023","journal-title":"J. Autoimmun."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"van Splunter, M., van Osch, T.L.J., Brugman, S., Savelkoul, H.F.J., Joosten, L.A.B., Netea, M.G., and van Neerven, R.J.J. (2018). Induction of Trained Innate Immunity in Human Monocytes by Bovine Milk and Milk-Derived Immunoglobulin G. Nutrients, 10.","DOI":"10.3390\/nu10101378"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Wang, J., Liu, Y.M., Hu, J., and Chen, C. (2023). Trained immunity in monocyte\/macrophage: Novel mechanism of phytochemicals in the treatment of atherosclerotic cardiovascular disease. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1109576"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"qiae240","DOI":"10.1093\/jleuko\/qiae240","article-title":"Interleukin-10 inhibits important components of trained immunity in human monocytes","volume":"117","author":"Scognamiglio","year":"2025","journal-title":"J. Leukoc. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e162581","DOI":"10.1172\/JCI162581","article-title":"Trained immunity is induced in humans after immunization with an adenoviral vector COVID-19 vaccine","volume":"133","author":"Murphy","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"111103","DOI":"10.1016\/j.isci.2024.111103","article-title":"Single high-fat challenge and trained innate immunity: A randomized controlled cross-over trial","volume":"27","author":"Bahrar","year":"2024","journal-title":"iScience"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s10875-025-01977-w","article-title":"Signatures of Trained Immunity Following mRNA Vaccination: Differences Between mRNA-1273 and BNT162b2","volume":"46","author":"Kunc","year":"2025","journal-title":"J. Clin. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.cell.2017.11.034","article-title":"Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity","volume":"172","author":"Mitroulis","year":"2018","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.cell.2020.09.058","article-title":"Innate Immune Training of Granulopoiesis Promotes Anti-tumor Activity","volume":"183","author":"Kalafati","year":"2020","journal-title":"Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1038\/s41422-025-01171-y","article-title":"Trained immunity: Induction of an inflammatory memory in disease","volume":"35","author":"Priem","year":"2025","journal-title":"Cell Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"eadf9904","DOI":"10.1126\/sciadv.adf9904","article-title":"Infection-experienced HSPCs protect against infections by generating neutrophils with enhanced mitochondrial bactericidal activity","volume":"9","author":"Darroch","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41581-022-00633-5","article-title":"Trained immunity-basic concepts and contributions to immunopathology","volume":"19","author":"Ochando","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.immuni.2023.12.005","article-title":"Multi-omics analysis of innate and adaptive responses to BCG vaccination reveals epigenetic cell states that predict trained immunity","volume":"57","author":"Moorlag","year":"2024","journal-title":"Immunity"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1016\/j.immuni.2024.08.018","article-title":"Antiviral innate immune memory in alveolar macrophages following SARS-CoV-2 infection ameliorates secondary influenza A virus disease","volume":"57","author":"Lercher","year":"2024","journal-title":"Immunity"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1016\/j.cell.2018.11.007","article-title":"Trained Immunity and Local Innate Immune Memory in the Lung","volume":"175","author":"Netea","year":"2018","journal-title":"Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2801","DOI":"10.1093\/cvr\/cvad003","article-title":"Bone marrow inflammatory memory in cardiometabolic disease and inflammatory comorbidities","volume":"119","author":"Mitroulis","year":"2024","journal-title":"Cardiovasc. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.ccell.2014.09.007","article-title":"Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity","volume":"26","author":"Broz","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.trecan.2024.12.003","article-title":"Recent developments in myeloid immune modulation in cancer therapy","volume":"11","author":"Parvanian","year":"2025","journal-title":"Trends Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.4049\/jimmunol.1901133","article-title":"Distinct Features of Human Myeloid Cell Cytokine Response Profiles Identify Neutrophil Activation by Cytokines as a Prognostic Feature during Tuberculosis and Cancer","volume":"204","author":"Devlin","year":"2020","journal-title":"J. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Oberg, H.H., Wesch, D., Kalyan, S., and Kabelitz, D. (2019). Regulatory Interactions Between Neutrophils, Tumor Cells and T Cells. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01690"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.it.2015.11.008","article-title":"Neutrophils in the Tumor Microenvironment","volume":"37","author":"Powell","year":"2016","journal-title":"Trends Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1146\/annurev.me.28.020177.002421","article-title":"BCG as adjuvant immunotherapy for neoplasia","volume":"28","author":"Hersh","year":"1977","journal-title":"Annu. Rev. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1007\/s00262-018-2234-9","article-title":"Beta-glucan-induced inflammatory monocytes mediate antitumor efficacy in the murine lung","volume":"67","author":"Alexander","year":"2018","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"110393","DOI":"10.1016\/j.biopha.2020.110393","article-title":"Mechanisms of BCG in the treatment of bladder cancer-current understanding and the prospect","volume":"129","author":"Han","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"eadu0292","DOI":"10.1126\/sciadv.adu0292","article-title":"Systemically inducing trained immunity overcomes solid tumors\u2019 immunosuppressive microenvironment","volume":"12","author":"Priem","year":"2026","journal-title":"Sci. Adv."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.ccr.2011.08.012","article-title":"Tumor entrained neutrophils inhibit seeding in the premetastatic lung","volume":"20","author":"Granot","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/s41422-025-01145-0","article-title":"Human myelocyte and metamyelocyte-stage neutrophils suppress tumor immunity and promote cancer progression","volume":"35","author":"Liu","year":"2025","journal-title":"Cell Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"eadf6493","DOI":"10.1126\/science.adf6493","article-title":"Deterministic reprogramming of neutrophils within tumors","volume":"383","author":"Ng","year":"2024","journal-title":"Science"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/s41568-022-00547-1","article-title":"A timeline of tumour-associated macrophage biology","volume":"23","author":"Cassetta","year":"2023","journal-title":"Nat. Rev. Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"102984","DOI":"10.1016\/j.copbio.2023.102984","article-title":"Tissue-resident macrophages\u2014Early passengers or drivers in the tumor niche?","volume":"83","author":"Vogel","year":"2023","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13045-019-0760-3","article-title":"Tumor-associated macrophages in tumor metastasis: Biological roles and clinical therapeutic applications","volume":"12","author":"Lin","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"101041","DOI":"10.1016\/j.drup.2023.101041","article-title":"The promising role of tumor-associated macrophages in the treatment of cancer","volume":"73","author":"Wang","year":"2024","journal-title":"Drug Resist. Updates"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Khan, S.U., Khan, M.U., Azhar Ud Din, M., Khan, I.M., Khan, M.I., Bungau, S., and Hassan, S.S.U. (2023). Reprogramming tumor-associated macrophages as a unique approach to target tumor immunotherapy. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1166487"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1016\/j.cmet.2021.09.002","article-title":"Tumor-derived exosomes drive immunosuppressive macrophages in a pre-metastatic niche through glycolytic dominant metabolic reprogramming","volume":"33","author":"Morrissey","year":"2021","journal-title":"Cell Metab."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1016\/j.cell.2021.02.048","article-title":"Genetically engineered myeloid cells rebalance the core immune suppression program in metastasis","volume":"184","author":"Kaczanowska","year":"2021","journal-title":"Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41590-022-01388-8","article-title":"Inducing trained immunity in pro-metastatic macrophages to control tumor metastasis","volume":"24","author":"Ding","year":"2023","journal-title":"Nat. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/s41467-022-28407-4","article-title":"The induction of peripheral trained immunity in the pancreas incites anti-tumor activity to control pancreatic cancer progression","volume":"13","author":"Geller","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1097\/XCS.0000000000001291","article-title":"Irreversible Electroporation and Beta-Glucan-Induced Trained Innate Immunity for Treatment of Pancreatic Ductal Adenocarcinoma: A Phase II Study","volume":"240","author":"Martin","year":"2025","journal-title":"J. Am. Coll. Surg."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/s41423-023-01015-y","article-title":"Good and bad outcomes of respiratory viral infections-influenza A virus trains sustained antitumor immunity of macrophages in the lung","volume":"20","author":"Frentzel","year":"2023","journal-title":"Cell. Mol. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/s41590-023-01428-x","article-title":"Influenza-trained mucosal-resident alveolar macrophages confer long-term antitumor immunity in the lungs","volume":"24","author":"Wang","year":"2023","journal-title":"Nat. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1016\/j.ccell.2021.10.009","article-title":"Single-cell analysis of human non-small cell lung cancer lesions refines tumor classification and patient stratification","volume":"39","author":"Leader","year":"2021","journal-title":"Cancer Cell"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/1479-5876-12-108","article-title":"A phase \u0399I study of five peptides combination with oxaliplatin-based chemotherapy as a first-line therapy for advanced colorectal cancer (FXV study)","volume":"12","author":"Hazama","year":"2014","journal-title":"J. Transl. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.clim.2016.03.015","article-title":"Phase I clinical trial of a five-peptide cancer vaccine combined with cyclophosphamide in advanced solid tumors","volume":"166\u2013167","author":"Murahashi","year":"2016","journal-title":"Clin. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1007\/s00384-020-03593-z","article-title":"Tumor-associated macrophage infiltration and prognosis in colorectal cancer: Systematic review and meta-analysis","volume":"35","author":"Li","year":"2020","journal-title":"Int. J. Colorectal Dis."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e2305081","DOI":"10.1002\/advs.202305081","article-title":"Engineered Probiotic-Based Personalized Cancer Vaccine Potentiates Antitumor Immunity through Initiating Trained Immunity","volume":"11","author":"Chen","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1038\/s41467-026-68466-5","article-title":"Leveraging glucan-induced trained immunity for the epigenetic and metabolic rewiring of macrophages to enhance colorectal cancer vaccine response","volume":"17","author":"Hamdan","year":"2026","journal-title":"Nat. Commun."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Bhargavi, G., and Subbian, S. (2024). The causes and consequences of trained immunity in myeloid cells. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1365127"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nri1785","article-title":"Neutrophils and immunity: Challenges and opportunities","volume":"6","author":"Nathan","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/imr.13142","article-title":"The role of neutrophils in trained immunity","volume":"314","author":"Kalafati","year":"2022","journal-title":"Immunol. Rev."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"0365","DOI":"10.34133\/research.0365","article-title":"Diabetes Primes Neutrophils for Neutrophil Extracellular Trap Formation through Trained Immunity","volume":"7","author":"Shrestha","year":"2024","journal-title":"Research"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/s41590-025-02099-6","article-title":"Author Correction: \u03b2-Glucan reprograms neutrophils to promote disease tolerance against influenza A virus","volume":"26","author":"Khan","year":"2025","journal-title":"Nat. Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12964-025-02098-y","article-title":"Dysregulation of neutrophil in sepsis: Recent insights and advances","volume":"23","author":"Zhang","year":"2025","journal-title":"Cell Commun. Signal."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1038\/s41590-023-01490-5","article-title":"Neutrophils and emergency granulopoiesis drive immune suppression and an extreme response endotype during sepsis","volume":"24","author":"Kwok","year":"2023","journal-title":"Nat. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.21037\/jtd.2019.12.63","article-title":"The complete blood count to diagnose septic shock","volume":"12","author":"Farkas","year":"2020","journal-title":"J. Thorac. Dis."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1164\/rccm.201606-1143OC","article-title":"Early Expansion of Circulating Granulocytic Myeloid-derived Suppressor Cells Predicts Development of Nosocomial Infections in Patients with Sepsis","volume":"196","author":"Uhel","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"eaax4517","DOI":"10.1126\/scitranslmed.aax4517","article-title":"BCG vaccination-induced emergency granulopoiesis provides rapid protection from neonatal sepsis","volume":"12","author":"Brook","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.cell.2017.12.031","article-title":"BCG Educates Hematopoietic Stem Cells to Generate Protective Innate Immunity against Tuberculosis","volume":"172","author":"Kaufmann","year":"2018","journal-title":"Cell"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Ning, H., Kang, J., Lu, Y., Liang, X., Zhou, J., Ren, R., Zhou, S., Zhao, Y., Xie, Y., and Bai, L. (2022). Cyclic di-AMP as endogenous adjuvant enhanced BCG-induced trained immunity and protection against Mycobacterium tuberculosis in mice. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.943667"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/s41577-020-0337-y","article-title":"BCG-induced trained immunity: Can it offer protection against COVID-19?","volume":"20","author":"Netea","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.chom.2020.05.014","article-title":"BCG Vaccination in Humans Elicits Trained Immunity via the Hematopoietic Progenitor Compartment","volume":"28","author":"Cirovic","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4724","DOI":"10.1038\/s41467-024-48796-y","article-title":"Neutrophils and galectin-3 defend mice from lethal bacterial infection and humans from acute respiratory failure","volume":"15","author":"Das","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Dagenais, A., Villalba-Guerrero, C., and Olivier, M. (2023). Trained immunity: A \u201cnew\u201d weapon in the fight against infectious diseases. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1147476"},{"key":"ref_107","first-page":"745","article-title":"Monocyte\/macrophage-mediated trained immunity in disease prevention and immunotherapy","volume":"59","author":"Zhang","year":"2026","journal-title":"Bioact. Mater."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"107791","DOI":"10.1016\/j.intimp.2021.107791","article-title":"The roles of macrophage polarization in the host immune response to sepsis","volume":"96","author":"Chen","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Ji, F., Zhang, L., Ning, L., Zhang, M., and Zhang, J. (2026). Crosstalk of mitochondrial dysfunction and macrophage polarization in sepsis. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1692597"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.ejim.2023.12.020","article-title":"Enduring echoes: Post-infectious long-term changes in innate immunity","volume":"123","author":"Dulfer","year":"2024","journal-title":"Eur. J. Intern. Med."},{"key":"ref_111","first-page":"56","article-title":"Sepsis-induced immunosuppression: Mechanisms, diagnosis and current treatment options","volume":"9","author":"Liu","year":"2022","journal-title":"Mil. Med. Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"5258","DOI":"10.7150\/ijbs.115515","article-title":"Recent Advances of Trained immunity in Macrophages","volume":"21","author":"Li","year":"2025","journal-title":"Int. J. Biol. Sci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1146\/annurev-virology-091919-072546","article-title":"Shifting the Immune Memory Paradigm: Trained Immunity in Viral Infections","volume":"9","author":"Taks","year":"2022","journal-title":"Annu. Rev. Virol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.1007\/s10753-024-02033-2","article-title":"Oroxylin A-induced Trained Immunity Promotes LC3-associated Phagocytosis in Macrophage in Protecting Mice Against Sepsis","volume":"47","author":"Yin","year":"2024","journal-title":"Inflammation"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e04101","DOI":"10.1002\/advs.202504101","article-title":"BCG-Derived Outer Membrane Vesicles Induce TLR2-Dependent Trained Immunity to Protect Against Polymicrobial Sepsis","volume":"12","author":"Gong","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.chom.2017.12.010","article-title":"BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity","volume":"23","author":"Arts","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"114849","DOI":"10.1016\/j.celrep.2024.114849","article-title":"LPS-induced lung tissue-resident trained innate immunity provides differential protection against pneumococci and SARS-CoV-2","volume":"43","author":"Kang","year":"2024","journal-title":"Cell Rep."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1007\/s00011-024-01946-w","article-title":"Trained immunity of synovial macrophages is associated with exacerbated joint inflammation and damage after Staphylococcus aureus infection","volume":"73","author":"Rocha","year":"2024","journal-title":"Inflamm. Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e134073","DOI":"10.1172\/JCI134073","article-title":"Hypoxia drives murine neutrophil protein scavenging to maintain central carbon metabolism","volume":"131","author":"Watts","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"108387","DOI":"10.1016\/j.celrep.2020.108387","article-title":"BCG Vaccination Induces Long-Term Functional Reprogramming of Human Neutrophils","volume":"33","author":"Moorlag","year":"2020","journal-title":"Cell Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41590-025-02380-8","article-title":"Author Correction: Hypoxia induces histone clipping and H3K4me3 loss in neutrophil progenitors resulting in long-term impairment of neutrophil immunity","volume":"27","author":"Sadiku","year":"2026","journal-title":"Nat. Immunol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.cmet.2020.11.016","article-title":"Neutrophils Fuel Effective Immune Responses through Gluconeogenesis and Glycogenesis","volume":"33","author":"Sadiku","year":"2021","journal-title":"Cell Metab."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1084\/jem.20040624","article-title":"Hypoxia-induced neutrophil survival is mediated by HIF-1alpha-dependent NF-kappaB activity","volume":"201","author":"Walmsley","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Lampiasi, N., and Russo, R. (2026). HIF-1\u03b1 as a Central Regulator of Monocyte Responses to Hypoxia. Biology, 15.","DOI":"10.3390\/biology15030213"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.cmet.2016.10.008","article-title":"Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity","volume":"24","author":"Arts","year":"2016","journal-title":"Cell Metab."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"107170","DOI":"10.1016\/j.phrs.2024.107170","article-title":"SARS-CoV-2 mitochondrial metabolic and epigenomic reprogramming in COVID-19","volume":"204","author":"Guarnieri","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s00281-024-01015-8","article-title":"Metabolic Regulation in the Induction of Trained Immunity","volume":"46","author":"Ferreira","year":"2024","journal-title":"Semin. Immunopathol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1038\/s42255-024-01183-9","article-title":"Author Correction: PNPO-PLP axis senses prolonged hypoxia in macrophages by regulating lysosomal activity","volume":"6","author":"Sekine","year":"2024","journal-title":"Nat. Metab."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"e16052","DOI":"10.7717\/peerj.16052","article-title":"Molecular and phenotypic distinctions of macrophages in tolerant and susceptible to hypoxia rats","volume":"11","author":"Dzhalilova","year":"2023","journal-title":"PeerJ"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.cmet.2022.12.005","article-title":"Metabolic adaptation supports enhanced macrophage efferocytosis in limited-oxygen environments","volume":"35","author":"Wang","year":"2023","journal-title":"Cell Metab."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/s44161-024-00462-8","article-title":"Stroke and myocardial infarction induce neutrophil extracellular trap release disrupting lymphoid organ structure and immunoglobulin secretion","volume":"3","author":"Tuz","year":"2024","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1038\/s41467-020-16191-y","article-title":"Neutrophil extracellular traps released by neutrophils impair revascularization and vascular remodeling after stroke","volume":"11","author":"Kang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s00395-025-01111-2","article-title":"The cGAS-STING pathway promotes acute ischemia-induced neutropoiesis and neutrophil priming in the bone marrow","volume":"120","author":"Zhu","year":"2025","journal-title":"Basic Res. Cardiol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.scib.2024.02.003","article-title":"Single-cell profile reveals the landscape of cardiac immunity and identifies a cardio-protective Ym-1(hi) neutrophil in myocardial ischemia-reperfusion injury","volume":"69","author":"Dong","year":"2024","journal-title":"Sci. Bull."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1161\/ATVBAHA.121.317197","article-title":"Ischemic-Trained Monocytes Improve Arteriogenesis in a Mouse Model of Hindlimb Ischemia","volume":"42","author":"Barboza","year":"2022","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/j.jcmgh.2023.01.004","article-title":"Gut Microbiota-Derived Glutamine Attenuates Liver Ischemia\/Reperfusion Injury via Macrophage Metabolic Reprogramming","volume":"15","author":"Lu","year":"2023","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1016\/j.cmet.2020.05.004","article-title":"Endothelial Lactate Controls Muscle Regeneration from Ischemia by Inducing M2-like Macrophage Polarization","volume":"31","author":"Zhang","year":"2020","journal-title":"Cell Metab."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41418-023-01252-8","article-title":"TREM2 macrophage promotes cardiac repair in myocardial infarction by reprogramming metabolism via SLC25A53","volume":"31","author":"Gong","year":"2024","journal-title":"Cell Death Differ."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1093\/eurheartj\/ehaf982","article-title":"Trained immunity in cardiovascular disease","volume":"47","author":"Riksen","year":"2026","journal-title":"Eur. Heart J."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1093\/eurheartj\/ehae024","article-title":"\u2018Training\u2019 of innate immunity following myocardial infarction exacerbates atherosclerosis","volume":"45","author":"Natarajan","year":"2024","journal-title":"Eur. Heart J."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/9\/752\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T09:18:43Z","timestamp":1776935923000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/9\/752"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,23]]},"references-count":140,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["cells15090752"],"URL":"https:\/\/doi.org\/10.3390\/cells15090752","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,23]]}}}