{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:01:05Z","timestamp":1790596865840,"version":"4.1.0"},"reference-count":100,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"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>Breakthroughs in cancer immunotherapy have been overwhelmingly driven by advances in adaptive immunity, leaving the therapeutic potential of innate immunity largely untapped, a gap in the current treatment paradigm. Trained immunity, defined by the durable, mitotically maintained metabolic and epigenetic memory that innate immune cells acquire after transient stimulation, offers a new approach to addressing this deficit. Here we survey the triggering signals, cellular heterogeneity, and molecular circuitry that govern trained immunity within the tumor microenvironment. We dissect its dualistic character: the mechanistic basis by which trained immunity can either restrain or promote tumor progression, and what this ambivalence means for the design of next-generation immunotherapies. These insights inform a growing pipeline of trained-immunity-based cancer vaccines, which we categorize into four engineered platforms, recombinant BCG, \u03b2-glucan nanoformulations, lipid nanoparticle (LNP)-mRNA bifunctional vaccines, and commensal-derived adjuvants. We further propose that vaccine efficacy may depend in part on host immune context, and outline stratification strategies and dosing schedules that may need to be adjusted according to individual immune status, pending clinical validation. In aggregate, evidence from human bladder cancer, preclinical tumor models, and non-tumor trained immunity studies suggests that trained immunity could elevate innate immunity from a supporting role toward an independent therapeutic axis, although most of its direct cancer applications remain at the preclinical or conceptual stage.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1939256","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:28:13Z","timestamp":1790594893000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Trained immunity in cancer immunotherapy and vaccine development: mechanisms, evidence gaps, and translational opportunities"],"prefix":"10.3389","volume":"17","author":[{"given":"Lian","family":"Yang","sequence":"first","affiliation":[{"name":"Affiliated Hospital of Xiangnan University","place":["Chenzhou, Hunan, China"]},{"name":"Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shufei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"He","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxu","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University","place":["Guangzhou, China"]},{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghui","family":"Tan","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Xiangnan University","place":["Chenzhou, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/25785826.2024.2438426","article-title":"Therapeutic potential of trained immunity for malignant disease","volume":"48","author":"Takahashi","year":"2025","journal-title":"Immunol Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1186\/s13046-025-03519-z","article-title":"Immunotherapy resistance in non-small cell lung cancer: from mechanisms to therapeutic opportunities","volume":"44","author":"Wang","year":"2025","journal-title":"J Exp Clin Cancer Res"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2026.1782830","article-title":"Trained immunity in cancer and autoimmunity: a double-edged sword in immune memory reprogramming","volume":"17","author":"Salari","year":"2026","journal-title":"Front Immunol"},{"key":"B4","doi-asserted-by":"publisher","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":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2011.04.006","article-title":"Trained immunity: a memory for innate host defense","volume":"9","author":"Netea","year":"2011","journal-title":"Cell Host Microbe"},{"key":"B6","doi-asserted-by":"publisher","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":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-020-01915-w","article-title":"Rewiring of glucose metabolism defines trained immunity induced by oxidized low-density lipoprotein","volume":"98","author":"Keating","year":"2020","journal-title":"J Mol Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2025.06.010","article-title":"Central trained immunity in the context of bladder cancer immunotherapy","volume":"43","author":"Chronopoulos","year":"2025","journal-title":"Cancer Cell"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-020-0346-4","article-title":"Trained immunity as a molecular mechanism for BCG immunotherapy in bladder cancer","volume":"17","author":"van Puffelen","year":"2020","journal-title":"Nat Rev Urol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-102119-073855","article-title":"Trained immunity: reprogramming innate immunity in health and disease","volume":"39","author":"Bekkering","year":"2021","journal-title":"Annu Rev Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0402-5","article-title":"Hematopoietic progenitor cells as integrative hubs for adaptation to and fine-tuning of inflammation","volume":"20","author":"Chavakis","year":"2019","journal-title":"Nat Immunol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1634","DOI":"10.1016\/j.cell.2018.09.042","article-title":"Induction of autonomous memory alveolar macrophages requires T cell help and is critical to trained immunity","volume":"175","author":"Chavakis","year":"2018","journal-title":"Cell"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-0291-z","article-title":"Targeting immunometabolism as an anti-inflammatory strategy","volume":"30","author":"Palsson-McDermott","year":"2020","journal-title":"Cell Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.114.303887","article-title":"Oxidized low-density lipoprotein induces long-term proinflammatory cytokine production and foam cell formation via epigenetic reprogramming of monocytes","volume":"34","author":"Bekkering","year":"2014","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202500802R","article-title":"Trained immunity induced by oxidized low-density lipoprotein is dependent on glutaminolysis","volume":"39","author":"Bekkering","year":"2025","journal-title":"FASEB J"},{"key":"B16","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1146\/annurev-immunol-032712-100008","article-title":"Immunogenic cell death in cancer therapy","volume":"31","author":"Kroemer","year":"2013","journal-title":"Annu Rev Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nature13490","article-title":"Functional polarization of tumour-associated macrophages by tumour-derived lactic acid","volume":"513","author":"Kroemer","year":"2014","journal-title":"Nature"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1678-1","article-title":"Metabolic regulation of gene expression by histone lactylation","volume":"574","author":"Colegio","year":"2019","journal-title":"Nature"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-025-01542-w","article-title":"Trained immunity induced by DAMPs and LAMPs in chronic inflammatory diseases","volume":"57","author":"Kim","year":"2025","journal-title":"Exp Mol Med"},{"key":"B20","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/nri.2016.107","article-title":"Immunogenic cell death in cancer and infectious disease","volume":"17","author":"Galluzzi","year":"2017","journal-title":"Nat Rev Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/s41590-022-01132-2","article-title":"Immunogenic cell stress and death","volume":"23","author":"Kroemer","year":"2022","journal-title":"Nat Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(09)70082-8","article-title":"Systemic effects of local radiotherapy","volume":"10","author":"Formenti","year":"2009","journal-title":"Lancet Oncol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1016\/j.cell.2020.09.059","article-title":"Trained immunity-promoting nanobiologic therapy suppresses tumor growth and potentiates checkpoint inhibition","volume":"183","author":"Priem","year":"2020","journal-title":"Cell"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1665099","article-title":"The significance of trained immunity in cancer","volume":"16","author":"Qu","year":"2025","journal-title":"Front Immunol"},{"key":"B25","doi-asserted-by":"publisher","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":"B26","doi-asserted-by":"publisher","DOI":"10.1172\/jci147719","article-title":"Single-cell RNA sequencing reveals induction of distinct trained-immunity programs in human monocytes","volume":"132","author":"Zhang","year":"2022","journal-title":"J Clin Invest"},{"key":"B27","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.gde.2009.11.004","article-title":"Inflammation and oncogenesis: a vicious connection","volume":"20","author":"Grivennikov","year":"2010","journal-title":"Curr Opin Genet Dev"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1365127","article-title":"The causes and consequences of trained immunity in myeloid cells","volume":"15","author":"Bhargavi","year":"2024","journal-title":"Front Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1126\/science.1250684","article-title":"mTOR- and HIF-1alpha-mediated aerobic glycolysis as metabolic basis for trained immunity","volume":"345","author":"Cheng","year":"2014","journal-title":"Science"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1016\/j.ccell.2025.05.002","article-title":"Microbial cancer immunotherapy reprograms hematopoiesis to enhance myeloid-driven antitumor immunity","volume":"43","author":"Daman","year":"2025","journal-title":"Cancer Cell"},{"key":"B31","doi-asserted-by":"publisher","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":"B32","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao4227","article-title":"Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice","volume":"361","author":"Albrengues","year":"2018","journal-title":"Science"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2014.10.005","article-title":"BCG-induced trained immunity in NK cells: role for non-specific protection from infection","volume":"155","author":"Kleinnijenhuis","year":"2014","journal-title":"Clin Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20120944","article-title":"Sustained effector function of IL-12\/15\/18-preactivated NK cells against established tumors","volume":"209","author":"Ni","year":"2012","journal-title":"J Exp Med"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1362289","article-title":"The cholera toxin B subunit induces trained immunity in dendritic cells and promotes CD8 T cell antitumor immunity","volume":"15","author":"Tepale-Segura","year":"2024","journal-title":"Front Immunol"},{"key":"B36","doi-asserted-by":"publisher","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":"B37","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/j.stem.2022.12.005","article-title":"C\/EBPbeta-dependent epigenetic memory induces trained immunity in hematopoietic stem cells","volume":"26","author":"de Laval","year":"2020","journal-title":"Cell Stem Cell"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2020.07.006","article-title":"OxLDL-mediated immunologic memory in endothelial cells","volume":"146","author":"Sohrabi","year":"2020","journal-title":"J Mol Cell Cardiol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3390\/medsci14020202","article-title":"From chronic inflammation to cancer: the role of trained immunity in IBD-associated colorectal carcinogenesis","volume":"14","author":"Sipos","year":"2026","journal-title":"Med Sci (Basel)"},{"key":"B40","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.cell.2010.03.014","article-title":"Macrophage diversity enhances tumor progression and metastasis","volume":"141","author":"Qian","year":"2010","journal-title":"Cell"},{"key":"B41","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.it.2010.10.002","article-title":"Molecular mechanisms of myeloid-derived suppressor cell expansion and function","volume":"21","author":"Condamine","year":"2011","journal-title":"Semin Cancer Biol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/nri2506","article-title":"Myeloid-derived suppressor cells as regulators of the immune system","volume":"9","author":"Gabrilovich","year":"2009","journal-title":"Nat Rev Immunol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1016\/j.cell.2020.09.062","article-title":"M. tuberculosis reprograms hematopoietic stem cells to limit myelopoiesis and impair trained immunity","volume":"183","author":"Khan","year":"2020","journal-title":"Cell"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/nri2506","article-title":"Myeloid-derived suppressor cells as regulators of the immune system","volume":"9","author":"Gabrilovich","year":"2009","journal-title":"Nat Rev Immunol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1016\/j.immuni.2026.03.001","article-title":"Molecular and cellular bases of trained immunity","volume":"59","author":"Sun","year":"2026","journal-title":"Immunity"},{"key":"B46","doi-asserted-by":"publisher","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":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/nature25986","article-title":"Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1","volume":"556","author":"Mills","year":"2018","journal-title":"Nature"},{"key":"B48","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/j.cell.2016.08.064","article-title":"Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages","volume":"167","author":"Mills","year":"2016","journal-title":"Cell"},{"key":"B49","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.cell.2017.11.025","article-title":"Metabolic induction of trained immunity through the mevalonate pathway","volume":"172","author":"Bekkering","year":"2018","journal-title":"Cell"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2024.116505","article-title":"Dietary sodium modulates mTORC1-dependent trained immunity in macrophages to accelerate CKD development","volume":"229","author":"Chen","year":"2024","journal-title":"Biochem Pharmacol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.cmet.2018.09.003","article-title":"The itaconate pathway is a central regulatory node linking innate immune tolerance and trained immunity","volume":"29","author":"Dom\u00ednguez-Andr\u00e9s","year":"2019","journal-title":"Cell Metab"},{"key":"B52","doi-asserted-by":"publisher","first-page":"111890","DOI":"10.1016\/j.celrep.2022.111890","article-title":"Akkermansia supplementation reverses the tumor-promoting effect of the fecal microbiota transplantation in ovarian cancer","volume":"41","author":"Wang","year":"2022","journal-title":"Cell Rep"},{"key":"B53","doi-asserted-by":"publisher","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":"B54","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1467052","article-title":"A novel hypoxia- and lactate metabolism-related prognostic signature to characterize the immune landscape and predict immunotherapy response in osteosarcoma","volume":"15","author":"Wang","year":"2024","journal-title":"Front Immunol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.03.048","article-title":"Long-term histone lactylation connects metabolic and epigenetic rewiring in innate immune memory","volume":"188","author":"Ziogas","year":"2025","journal-title":"Cell"},{"key":"B56","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1084\/jem.20151570","article-title":"Immunometabolism governs dendritic cell and macrophage function","volume":"213","author":"O'Neill","year":"2016","journal-title":"J Exp Med"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adr4458","article-title":"Succinate-loaded tumor cell-derived microparticles reprogram tumor-associated macrophage metabolism","volume":"17","author":"Lu","year":"2025","journal-title":"Sci Transl Med"},{"key":"B58","doi-asserted-by":"publisher","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":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0127-6","article-title":"Macrophages as regulators of tumour immunity and immunotherapy","volume":"19","author":"DeNardo","year":"2019","journal-title":"Nat Rev Immunol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2026.101647","article-title":"Human macrophages encode stimulus-specific information of prior exposures through trained immunity","volume":"17","author":"O'Farrell","year":"2026","journal-title":"Cell Syst"},{"key":"B61","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/nrclinonc.2016.217","article-title":"Tumour-associated macrophages as treatment targets in oncology","volume":"14","author":"Mantovani","year":"2017","journal-title":"Nat Rev Clin Oncol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-018-0059-4","article-title":"Inflammaging: a new immune-metabolic viewpoint for age-related diseases","volume":"14","author":"Franceschi","year":"2018","journal-title":"Nat Rev Endocrinol"},{"key":"B63","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1016\/j.cell.2020.09.058","article-title":"Innate immune training of granulopoiesis promotes antitumor activity","volume":"183","author":"Kalafati","year":"2020","journal-title":"Cell"},{"key":"B64","doi-asserted-by":"publisher","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":"B65","doi-asserted-by":"publisher","first-page":"2955","DOI":"10.1038\/s41467-019-10486-5","article-title":"Induction of memory-like dendritic cell responses in vivo","volume":"10","author":"Hole","year":"2019","journal-title":"Nat Commun"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c11658","article-title":"Targeted initiation of trained immunity in tumor-associated macrophages with membrane-camouflaged Bacillus Calmette-Gu\u00e9rin for lung carcinoma immunotherapy","volume":"18","author":"Zhang","year":"2024","journal-title":"ACS Nano"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70461","article-title":"Trained immunity in health and disease","volume":"6","author":"Yao","year":"2025","journal-title":"MedComm"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2025.12.044","article-title":"Monocyte\/macrophage-mediated trained immunity in disease prevention and immunotherapy","volume":"59","author":"Zhang","year":"2026","journal-title":"Bioact Mater"},{"key":"B69","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.cell.2017.12.013","article-title":"Western diet triggers NLRP3-dependent innate immune reprogramming","volume":"172","author":"Christ","year":"2018","journal-title":"Cell"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.011","article-title":"Role of the microbiota in immunity and inflammation","volume":"157","author":"Belkaid","year":"2014","journal-title":"Cell"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-025-01035-9","article-title":"The next generation of immunotherapies for lung cancers","volume":"22","author":"Zhao","year":"2025","journal-title":"Nat Rev Clin Oncol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08507-5","article-title":"A neoantigen vaccine generates antitumour immunity in renal cell carcinoma","volume":"640","author":"Braun","year":"2025","journal-title":"Nature"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2026.03.005","article-title":"Trained immunity responses across infectious diseases and cancer vaccines","volume":"137","author":"Fu","year":"2026","journal-title":"Trends Immunol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1097\/cm9.0000000000002890","article-title":"Research progress in the off-target effects of Bacille Calmette-Guerin vaccine","volume":"137","author":"Wu","year":"2024","journal-title":"Chin Med J (Engl)"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2025.05.014","article-title":"No (innate immune) training without lactate","volume":"85","author":"Van den Bossche","year":"2025","journal-title":"Mol Cell"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02616-20","article-title":"Designing the next generation of vaccines: relevance for future pandemics","volume":"11","author":"Dom\u00ednguez-Andr\u00e9s","year":"2020","journal-title":"mBio"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.3390\/cells15090752","article-title":"Trained immunity in neutrophils and mononuclear phagocytes: mechanisms and pathophysiological functions","volume":"15","author":"Li","year":"2026","journal-title":"Cells"},{"key":"B78","doi-asserted-by":"publisher","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":"B79","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adu0292","article-title":"Systemically inducing trained immunity overcomes solid tumors' immunosuppressive microenvironment","volume":"12","author":"Priem","year":"2026","journal-title":"Sci Adv"},{"key":"B80","doi-asserted-by":"publisher","first-page":"3054","DOI":"10.3390\/ijms26073119","article-title":"In vivo engineered CAR-T cell therapy: lessons built from COVID-19 mRNA vaccines","volume":"26","author":"Hamdan","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2025.114414","article-title":"Combination of ionizable lipids with oleic acid and vitamin E scaffolds for RNA cancer vaccine delivery","volume":"374","author":"Priem","year":"2026","journal-title":"J Control Release"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00526-x","article-title":"COVID-19 vaccines: modes of immune activation and future challenges","volume":"21","author":"Teijaro","year":"2021","journal-title":"Nat Rev Immunol"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-0090-8","article-title":"Engineering precision nanoparticles for drug delivery","volume":"20","author":"Mitchell","year":"2021","journal-title":"Nat Rev Drug Discov"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-050824-111031","article-title":"Myeloid cell reprogramming and immune suppression","volume":"88","author":"Grover","year":"2026","journal-title":"Annu Rev Physiol"},{"key":"B85","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s12943-025-02255-4","article-title":"The epigenetic hallmarks of immune cells in cancer","volume":"24","author":"Ji","year":"2025","journal-title":"Mol Cancer"},{"key":"B86","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1007\/s00203-026-04929-z","article-title":"mRNA vaccine development for tuberculosis: antigen design, immune mechanisms, and translational challenges","volume":"208","author":"Abuhassan","year":"2026","journal-title":"Arch Microbiol"},{"key":"B87","doi-asserted-by":"publisher","first-page":"2484386","DOI":"10.1186\/s12943-025-02255-4","article-title":"M28 family peptidase derived from Peribacillus frigoritolerans initiates trained immunity to prevent MRSA via the complosome-phosphatidylcholine axis","volume":"17","author":"Ji","year":"2025","journal-title":"Gut Microbes"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202504705","article-title":"A novel trained immunity adjuvant derived from commensal bacteria potentiates liposome-hydrogel cancer vaccine against breast tumors","volume":"15","author":"Zhou","year":"2026","journal-title":"Adv Healthc Mater"},{"key":"B89","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1007\/s00408-025-00801-x","article-title":"Update 2025: management of non-small-cell lung cancer","volume":"203","author":"Jeon","year":"2025","journal-title":"Lung"},{"key":"B90","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1002\/adhm.202504705","article-title":"Trained immunity: induction of an inflammatory memory in disease","volume":"35","author":"Schl\u00fcter","year":"2025","journal-title":"Cell Res"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2024.105703","article-title":"BCG's role in strengthening immune responses: implications for tuberculosis and comorbid diseases","volume":"127","author":"Yan","year":"2025","journal-title":"Infect Genet Evol"},{"key":"B92","doi-asserted-by":"publisher","first-page":"116202","DOI":"10.1007\/s00408-025-00801-x","article-title":"In vitro protocol demonstrating five functional steps of trained immunity in mice: implications on biomarker discovery and translational research","volume":"44","author":"Jeon","year":"2025","journal-title":"Cell Rep"},{"key":"B93","doi-asserted-by":"publisher","first-page":"1854","DOI":"10.3390\/cancers18010144","article-title":"Advances in neoantigen-based cancer vaccines","volume":"17","author":"Wu","year":"2025","journal-title":"Cancers (Basel)"},{"key":"B94","doi-asserted-by":"publisher","first-page":"102612","DOI":"10.1016\/j.arr.2026.103210","article-title":"Trained immunity in the treatment for haematological malignancy","volume":"97","author":"Liu","year":"2026","journal-title":"Ageing Res Rev"},{"key":"B95","doi-asserted-by":"publisher","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":"B96","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-026-60910-2","article-title":"Memory B cells in mature follicle-like tertiary lymphoid structures predict BCG response in non-muscle-invasive bladder cancer","volume":"18","author":"Wang","year":"2026","journal-title":"Sci Rep"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200442","article-title":"Divergent macrophage-regulated T cell states determine response to Bacillus Calmette-Guerin in high-risk bladder cancer","volume":"120","author":"Brown","year":"2026","journal-title":"J Clin Invest"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28509-z","article-title":"Re-engineered BCG overexpressing cyclic di-AMP augments trained immunity and exhibits improved antitumor efficacy","volume":"11","author":"Singh","year":"2023","journal-title":"J Immunother Cancer"},{"key":"B99","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1111\/imr.13326","article-title":"Trained immunity: General and emerging concepts","volume":"323","author":"Vuscan","year":"2024","journal-title":"Immunol Rev"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adf9556","article-title":"A protein-free vaccine stimulates innate immunity and protects against nosocomial pathogens","volume":"15","author":"Yan","year":"2023","journal-title":"Sci Transl Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1939256\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:28:14Z","timestamp":1790594894000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1939256\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,28]]},"references-count":100,"alternative-id":["10.3389\/fimmu.2026.1939256"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1939256","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,28]]},"article-number":"1939256"}}