{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:10:28Z","timestamp":1791807028266,"version":"4.3.4"},"reference-count":105,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T00:00:00Z","timestamp":1674518400000},"content-version":"unspecified","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"European Research Council","award":["833247"],"award-info":[{"award-number":["833247"]}]},{"name":"Romanian Ministry of European Funds","award":["103587"],"award-info":[{"award-number":["103587"]}]},{"name":"Romanian Ministry of European Funds","award":["P_37_762"],"award-info":[{"award-number":["P_37_762"]}]},{"name":"Netherlands Organization for Scientific Research","award":["184021007"],"award-info":[{"award-number":["184021007"]}]},{"name":"Integraal Kankercentrum Nederland","award":["2013-5926"],"award-info":[{"award-number":["2013-5926"]}]},{"name":"Integraal Kankercentrum Nederland","award":["2015-7914"],"award-info":[{"award-number":["2015-7914"]}]},{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"crossref","award":["APP1157556"],"award-info":[{"award-number":["APP1157556"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"crossref","award":["APP1173314"],"award-info":[{"award-number":["APP1173314"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NWO","award":["91717334"],"award-info":[{"award-number":["91717334"]}]},{"name":"NWO","award":["SPI 94-212"],"award-info":[{"award-number":["SPI 94-212"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2022,12,29]]},"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>BCG is recommended as intravesical immunotherapy to reduce the risk of tumor recurrence in patients with non-muscle invasive bladder cancer (NMIBC). Currently, it is unknown whether intravesical BCG application induces trained immunity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The aim of this research was to determine whether BCG immunotherapy induces trained immunity in NMIBC patients. We conducted a prospective observational cohort study in 17 NMIBC patients scheduled for BCG therapy and measured trained immunity parameters at 9 time points before and during a 1-year BCG maintenance regimen. Ex vivo cytokine production by peripheral blood mononuclear cells, epigenetic modifications, and changes in the monocyte transcriptome were measured. The frequency of respiratory infections was investigated in two larger cohorts of BCG-treated and non-BCG treated NMIBC patients as a surrogate measurement of trained immunity. Gene-based association analysis of genetic variants in candidate trained immunity genes and their association with recurrence-free survival and progression-free survival after BCG therapy was performed to investigate the hypothesized link between trained immunity and clinical response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that intravesical BCG does induce trained immunity based on an increased production of TNF and IL-1\u03b2 after heterologous ex vivo stimulation of circulating monocytes 6\u201312 weeks after intravesical BCG treatment; and a 37% decreased risk (OR 0.63 (95% CI 0.40 to 1.01)) for respiratory infections in BCG-treated versus non-BCG-treated NMIBC patients. An epigenomics approach combining chromatin immuno precipitation-sequencing and RNA-sequencing with in vitro trained immunity experiments identified enhanced inflammasome activity in BCG-treated individuals. Finally, germline variation in genes that affect trained immunity was associated with recurrence and progression after BCG therapy in NMIBC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We conclude that BCG immunotherapy induces trained immunity in NMIBC patients and this may account for the protective effects against respiratory infections. The data of our gene-based association analysis suggest that a link between trained immunity and oncological outcome may exist. Future studies should further investigate how trained immunity affects the antitumor immune responses in BCG-treated NMIBC patients<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2022-005518","type":"journal-article","created":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T09:35:17Z","timestamp":1674552917000},"page":"e005518","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":54,"title":["Intravesical BCG in patients with non-muscle invasive bladder cancer induces trained immunity and decreases respiratory infections"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3079-027X","authenticated-orcid":false,"given":"Jelmer H","family":"van Puffelen","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Radboudumc, Nijmegen, The Netherlands"},{"name":"Department for Health Evidence, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Novakovic","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Murdoch Children's Research Institute, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liesbeth","family":"van Emst","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Kooper","sequence":"additional","affiliation":[{"name":"Department of Urology, Erasmus MC Cancer Centre, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahlita C M","family":"Zuiverloon","sequence":"additional","affiliation":[{"name":"Department of Urology, Erasmus MC Cancer Centre, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula T H","family":"Oldenhof","sequence":"additional","affiliation":[{"name":"Department for Health Evidence, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0059-3857","authenticated-orcid":false,"given":"J Alfred","family":"Witjes","sequence":"additional","affiliation":[{"name":"Department of Urology, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessel E","family":"Galesloot","sequence":"additional","affiliation":[{"name":"Department for Health Evidence, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Vrieling","sequence":"additional","affiliation":[{"name":"Department for Health Evidence, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja K H","family":"Aben","sequence":"additional","affiliation":[{"name":"Department for Health Evidence, Radboudumc, Nijmegen, The Netherlands"},{"name":"IKNL, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lambertus A L M","family":"Kiemeney","sequence":"additional","affiliation":[{"name":"Department for Health Evidence, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egbert","family":"Oosterwijk","sequence":"additional","affiliation":[{"name":"Department of Urology, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai G","family":"Netea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboudumc, Nijmegen, The Netherlands"},{"name":"Department of Immunology and Metabolism, University of Bonn, Life & Medical Sciences Institute, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost L","family":"Boormans","sequence":"additional","affiliation":[{"name":"Department of Urology, Erasmus MC Cancer Centre, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine G","family":"van der Heijden","sequence":"additional","affiliation":[{"name":"Department of Urology, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo A B","family":"Joosten","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboudumc, Nijmegen, The Netherlands"},{"name":"Department of Medical Genetics, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sita H","family":"Vermeulen","sequence":"additional","affiliation":[{"name":"Department for Health Evidence, Radboudumc, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,1,24]]},"reference":[{"key":"2025100313210220000_11.1.e005518.1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.eururo.2021.08.010","article-title":"European association of urology guidelines on non-muscle-invasive bladder cancer (TA, T1, and carcinoma in situ)","volume":"81","author":"Babjuk","year":"2022","journal-title":"Eur Urol"},{"key":"2025100313210220000_11.1.e005518.2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2003.04655.x"},{"key":"2025100313210220000_11.1.e005518.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)64043-8"},{"key":"2025100313210220000_11.1.e005518.4","doi-asserted-by":"crossref","unstructured":"Matulay JT , Li R , Hensley PJ , et al . Contemporary outcomes of patients with nonmuscle-invasive bladder cancer treated with Bacillus Calmette-Gu\u00e9rin: implications for clinical trial design. J Urol 2021.doi:10.1097\/ju.0000000000001633","DOI":"10.1097\/JU.0000000000001633"},{"key":"2025100313210220000_11.1.e005518.5","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.eururo.2014.05.033","article-title":"The effect of age on the efficacy of maintenance bacillus Calmette-Gu\u00e9rin relative to maintenance epirubicin in patients with stage TA T1 urothelial bladder cancer: results from EORTC genito-urinary group study 30911","volume":"66","author":"Oddens","year":"2014","journal-title":"Eur Urol"},{"key":"2025100313210220000_11.1.e005518.6","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-003-0384-9"},{"key":"2025100313210220000_11.1.e005518.7","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1016\/S0022-5347(17)35678-1","article-title":"T-cell subsets required for intravesical BCG immunotherapy for bladder cancer","volume":"150","author":"Ratliff","year":"1993","journal-title":"J Urol"},{"key":"2025100313210220000_11.1.e005518.8","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.615091","article-title":"Immunological hallmarks for clinical response to BCG in bladder cancer","volume":"11","author":"Lim","year":"2020","journal-title":"Front Immunol"},{"key":"2025100313210220000_11.1.e005518.9","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1995.155"},{"key":"2025100313210220000_11.1.e005518.10","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(20010601)92:5<697::AID-IJC1245>3.0.CO;2-Z"},{"key":"2025100313210220000_11.1.e005518.11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00284"},{"key":"2025100313210220000_11.1.e005518.12","doi-asserted-by":"publisher","DOI":"10.1186\/1756-9966-32-87"},{"key":"2025100313210220000_11.1.e005518.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2013.10.012"},{"key":"2025100313210220000_11.1.e005518.14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2006.03191.x"},{"key":"2025100313210220000_11.1.e005518.15","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmq006"},{"key":"2025100313210220000_11.1.e005518.16","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.140942"},{"key":"2025100313210220000_11.1.e005518.17","doi-asserted-by":"publisher","DOI":"10.3399\/fimmu.2014.00603"},{"key":"2025100313210220000_11.1.e005518.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-00869-6"},{"key":"2025100313210220000_11.1.e005518.19","doi-asserted-by":"publisher","DOI":"10.1038\/nri2526"},{"key":"2025100313210220000_11.1.e005518.20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2010.01544.x"},{"key":"2025100313210220000_11.1.e005518.21","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12306"},{"key":"2025100313210220000_11.1.e005518.22","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.8.4238-4249.2003"},{"key":"2025100313210220000_11.1.e005518.23","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2017.00796","article-title":"Deconvolution of the response to Bacillus Calmette-Gu\u00e9rin reveals NF-\u03baB-Induced cytokines as autocrine mediators of innate immunity","volume":"8","author":"Bisiaux","year":"2017","journal-title":"Front Immunol"},{"key":"2025100313210220000_11.1.e005518.24","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0285-6"},{"key":"2025100313210220000_11.1.e005518.25","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf1098"},{"key":"2025100313210220000_11.1.e005518.26","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":"2025100313210220000_11.1.e005518.27","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.cell.2020.08.051","article-title":"Activate: randomized clinical trial of BCG vaccination against infection in the elderly","volume":"183","author":"Giamarellos-Bourboulis","year":"2020","journal-title":"Cell"},{"key":"2025100313210220000_11.1.e005518.28","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.amjms.2021.03.003","article-title":"Bacillus Calmette-Guerin vaccine and nonspecific immunity","volume":"361","author":"Parmar","year":"2021","journal-title":"Am J Med Sci"},{"key":"2025100313210220000_11.1.e005518.29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004485"},{"key":"2025100313210220000_11.1.e005518.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107634"},{"key":"2025100313210220000_11.1.e005518.31","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":"2025100313210220000_11.1.e005518.32","doi-asserted-by":"crossref","DOI":"10.1016\/j.micpath.2021.105088","article-title":"The role of IL-32 in Bacillus Calmette-Gu\u00e9rin (BCG)-induced trained immunity in infections caused by different Leishmania spp","volume":"158","author":"Silva","year":"2021","journal-title":"Microb Pathog"},{"key":"2025100313210220000_11.1.e005518.33","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1016\/j.celrep.2019.08.004","article-title":"\u03b2-Glucan-induced trained immunity protects against Leishmania braziliensis infection: a crucial role for IL-32","volume":"28","author":"Dos Santos","year":"2019","journal-title":"Cell Rep"},{"key":"2025100313210220000_11.1.e005518.34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1202870109"},{"key":"2025100313210220000_11.1.e005518.35","doi-asserted-by":"crossref","DOI":"10.1002\/cti2.1253","article-title":"Lysine methyltransferase G9a is an important modulator of trained immunity","volume":"10","author":"Mourits","year":"2021","journal-title":"Clin Transl Immunology"},{"key":"2025100313210220000_11.1.e005518.36","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1002\/eji.202149577","article-title":"An integrative genomics approach identifies KDM4 as a modulator of trained immunity","volume":"52","author":"Moorlag","year":"2022","journal-title":"Eur J Immunol"},{"key":"2025100313210220000_11.1.e005518.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.11.011"},{"key":"2025100313210220000_11.1.e005518.38","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":"2025100313210220000_11.1.e005518.39","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":"2025100313210220000_11.1.e005518.40","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-2042.2007.01696.x"},{"key":"2025100313210220000_11.1.e005518.41","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.00756.x"},{"key":"2025100313210220000_11.1.e005518.42","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.eururo.2015.06.023","article-title":"Cytokine panel for response to intravesical therapy (CyPRIT): nomogram of changes in urinary cytokine levels predicts patient response to Bacillus Calmette-Gu\u00e9rin","volume":"69","author":"Kamat","year":"2016","journal-title":"Eur Urol"},{"key":"2025100313210220000_11.1.e005518.43","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(01)66424-3"},{"key":"2025100313210220000_11.1.e005518.44","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-020-0346-4"},{"key":"2025100313210220000_11.1.e005518.45","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/BF01517205","article-title":"Bacillus Calmette-Guerin potentiates monocyte responses to lipopolysaccharide-induced tumor necrosis factor and interleukin-1, but not interleukin-6 in bladder cancer patients","volume":"38","author":"Conti","year":"1994","journal-title":"Cancer Immunology Immunotherapy"},{"key":"2025100313210220000_11.1.e005518.46","doi-asserted-by":"crossref","first-page":"356","DOI":"10.3349\/ymj.1993.34.4.356","article-title":"Production of tumor necrosis factor by intravesical administration of Bacillus Calmette Gu\u00e9rin in patients with superficial bladder cancer","volume":"34","author":"Kim","year":"1993","journal-title":"Yonsei Med J"},{"key":"2025100313210220000_11.1.e005518.47","doi-asserted-by":"publisher","DOI":"10.1159\/000355628"},{"key":"2025100313210220000_11.1.e005518.48","doi-asserted-by":"publisher","DOI":"10.1084\/jem.173.4.931"},{"key":"2025100313210220000_11.1.e005518.49","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"2025100313210220000_11.1.e005518.50","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq033"},{"key":"2025100313210220000_11.1.e005518.51","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1107s32"},{"key":"2025100313210220000_11.1.e005518.52","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2011-12-2-r13"},{"key":"2025100313210220000_11.1.e005518.53","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr490"},{"key":"2025100313210220000_11.1.e005518.54","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1016\/j.cell.2016.09.034","article-title":"\u03b2-Glucan reverses the epigenetic state of LPS-induced immunological tolerance","volume":"167","author":"Novakovic","year":"2016","journal-title":"Cell"},{"key":"2025100313210220000_11.1.e005518.55","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"2025100313210220000_11.1.e005518.56","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1630"},{"key":"2025100313210220000_11.1.e005518.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.05.004"},{"key":"2025100313210220000_11.1.e005518.58","doi-asserted-by":"crossref","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":"2025100313210220000_11.1.e005518.59","doi-asserted-by":"crossref","DOI":"10.1016\/j.xpro.2021.100365","article-title":"In\u00a0vitro induction of trained immunity in adherent human monocytes","volume":"2","author":"Dom\u00ednguez-Andr\u00e9s","year":"2021","journal-title":"STAR Protoc"},{"key":"2025100313210220000_11.1.e005518.60","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abn4002","article-title":"Neonatal BCG vaccination is associated with a long-term DNA methylation signature in circulating monocytes","volume":"8","author":"Bannister","year":"2022","journal-title":"Sci Adv"},{"key":"2025100313210220000_11.1.e005518.61","doi-asserted-by":"crossref","DOI":"10.1186\/s12885-020-06954-7","article-title":"Insight into bladder cancer care: study protocol of a large nationwide prospective cohort study (BlaZIB)","volume":"20","author":"Ripping","year":"2020","journal-title":"BMC Cancer"},{"key":"2025100313210220000_11.1.e005518.62","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-030396"},{"key":"2025100313210220000_11.1.e005518.63","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr303"},{"key":"2025100313210220000_11.1.e005518.64","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.174"},{"key":"2025100313210220000_11.1.e005518.65","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.20610"},{"key":"2025100313210220000_11.1.e005518.66","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0089164"},{"key":"2025100313210220000_11.1.e005518.67","doi-asserted-by":"crossref","first-page":"5603","DOI":"10.1172\/JCI133934","article-title":"Circadian rhythm influences induction of trained immunity by BCG vaccination","volume":"130","author":"de Bree","year":"2020","journal-title":"J Clin Invest"},{"key":"2025100313210220000_11.1.e005518.68","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-00845-6"},{"key":"2025100313210220000_11.1.e005518.69","doi-asserted-by":"crossref","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":"2025100313210220000_11.1.e005518.70","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2019.00002","article-title":"Lnc-ing trained immunity to chromatin architecture","volume":"7","author":"Fanucchi","year":"2019","journal-title":"Front Cell Dev Biol"},{"key":"2025100313210220000_11.1.e005518.71","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1007\/s10753-018-0834-3","article-title":"Cidec is involved in LPS-induced inflammation and apoptosis in renal tubular epithelial cells","volume":"41","author":"He","year":"2018","journal-title":"Inflammation"},{"key":"2025100313210220000_11.1.e005518.72","doi-asserted-by":"crossref","first-page":"231","DOI":"10.3892\/ijmm_00000457","article-title":"Identification of lipid droplet-associated proteins in the formation of macrophage-derived foam cells using microarrays","volume":"26","author":"Li","year":"2010","journal-title":"Int J Mol Med"},{"key":"2025100313210220000_11.1.e005518.73","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6949"},{"key":"2025100313210220000_11.1.e005518.74","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.celrep.2016.09.050","article-title":"ATF7IP-mediated stabilization of the histone methyltransferase SETDB1 is essential for heterochromatin formation by the HUSH complex","volume":"17","author":"Timms","year":"2016","journal-title":"Cell Rep"},{"key":"2025100313210220000_11.1.e005518.75","doi-asserted-by":"crossref","DOI":"10.15252\/embr.201948297","article-title":"ATF7IP regulates SETDB1 nuclear localization and increases its ubiquitination","volume":"20","author":"Tsusaka","year":"2019","journal-title":"EMBO Rep"},{"key":"2025100313210220000_11.1.e005518.76","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.exphem.2015.08.013","article-title":"Fanca safeguards interphase and mitosis during hematopoiesis in vivo","volume":"43","author":"Abdul-Sater","year":"2015","journal-title":"Exp Hematol"},{"key":"2025100313210220000_11.1.e005518.77","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.237"},{"key":"2025100313210220000_11.1.e005518.78","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3119"},{"key":"2025100313210220000_11.1.e005518.79","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16889-z"},{"key":"2025100313210220000_11.1.e005518.80","doi-asserted-by":"crossref","unstructured":"Santos JC , Dick MS , Lagrange B , et al . LPS targets host guanylate\u2010binding proteins to the bacterial outer membrane for non\u2010canonical inflammasome activation. Embo J 2018;37.doi:10.15252\/embj.201798089","DOI":"10.15252\/embj.201798089"},{"key":"2025100313210220000_11.1.e005518.81","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.4MR0516-223R"},{"key":"2025100313210220000_11.1.e005518.82","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3118"},{"key":"2025100313210220000_11.1.e005518.83","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2017.10.005"},{"key":"2025100313210220000_11.1.e005518.84","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2016.2583"},{"key":"2025100313210220000_11.1.e005518.85","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.6.4086"},{"key":"2025100313210220000_11.1.e005518.86","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12193"},{"key":"2025100313210220000_11.1.e005518.87","doi-asserted-by":"crossref","DOI":"10.1098\/rsos.202333","article-title":"RUFY4 exists as two translationally regulated isoforms, that localize to the mitochondrion in activated macrophages","volume":"8","author":"Vale\u010dka","year":"2021","journal-title":"R Soc Open Sci"},{"key":"2025100313210220000_11.1.e005518.88","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1080\/15548627.2015.1136772","article-title":"RUFY4: immunity piggybacking on autophagy?","volume":"12","author":"Terawaki","year":"2016","journal-title":"Autophagy"},{"key":"2025100313210220000_11.1.e005518.89","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201501059"},{"key":"2025100313210220000_11.1.e005518.90","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201848070"},{"key":"2025100313210220000_11.1.e005518.91","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.celrep.2018.06.012","article-title":"Constitutive interferon maintains GBP expression required for release of bacterial components upstream of pyroptosis and anti-DNA responses","volume":"24","author":"Liu","year":"2018","journal-title":"Cell Rep"},{"key":"2025100313210220000_11.1.e005518.92","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ144"},{"key":"2025100313210220000_11.1.e005518.93","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv332"},{"key":"2025100313210220000_11.1.e005518.94","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2019.04.020"},{"key":"2025100313210220000_11.1.e005518.95","doi-asserted-by":"crossref","first-page":"E412","DOI":"10.5489\/cuaj.7066","article-title":"Innate immune memory is associated with increased disease-free survival in bladder cancer patients treated with Bacillus Calmette-Gu\u00e9rin","volume":"15","author":"Graham","year":"2021","journal-title":"Can Urol Assoc J"},{"key":"2025100313210220000_11.1.e005518.96","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00688-13"},{"key":"2025100313210220000_11.1.e005518.97","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/s41585-021-00481-1","article-title":"100 years of Bacillus Calmette-Gu\u00e9rin immunotherapy: from cattle to COVID-19","volume":"18","author":"Lobo","year":"2021","journal-title":"Nat Rev Urol"},{"key":"2025100313210220000_11.1.e005518.98","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1002\/bco2.21","article-title":"The role of the urologist, BCG vaccine administration, and SARS-CoV-2: an overview","volume":"1","author":"Brooks","year":"2020","journal-title":"BJUI Compass"},{"key":"2025100313210220000_11.1.e005518.99","doi-asserted-by":"crossref","first-page":"5591","DOI":"10.1172\/JCI133935","article-title":"BCG vaccination in humans inhibits systemic inflammation in a sex-dependent manner","volume":"130","author":"Koeken","year":"2020","journal-title":"J Clin Invest"},{"key":"2025100313210220000_11.1.e005518.100","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3001765","article-title":"Plasma metabolome predicts trained immunity responses after antituberculosis BCG vaccination","volume":"20","author":"Koeken","year":"2022","journal-title":"PLoS Biol"},{"key":"2025100313210220000_11.1.e005518.101","doi-asserted-by":"publisher","DOI":"10.1126\/science.1217141"},{"key":"2025100313210220000_11.1.e005518.102","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20171749"},{"key":"2025100313210220000_11.1.e005518.103","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/s41580-020-0244-x","article-title":"Molecular mechanisms and cellular functions of cGAS-STING signalling","volume":"21","author":"Hopfner","year":"2020","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2025100313210220000_11.1.e005518.104","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28509-z"},{"key":"2025100313210220000_11.1.e005518.105","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3233\/BLC-150027","article-title":"Independent replication of published germline polymorphisms associated with urinary bladder cancer prognosis and treatment response","volume":"2","author":"Grotenhuis","year":"2016","journal-title":"Bladder Cancer"}],"updated-by":[{"DOI":"10.1136\/jitc-2022-005518corr1","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000}}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2022-005518","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T20:21:14Z","timestamp":1759522874000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2022-005518"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1]]},"references-count":105,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1,24]]},"published-print":{"date-parts":[[2023,1]]}},"alternative-id":["10.1136\/jitc-2022-005518"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2022-005518","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.02.21.480081","asserted-by":"object"}]},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1]]}}}