{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:16:57Z","timestamp":1787026617918,"version":"build-2736575974"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T00:00:00Z","timestamp":1728518400000},"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:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The intricate roles of immune cells and inflammatory factors in cancer, particularly their association with the risk of bladder cancer, are not well understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study aimed to clarify potential causal relationships between these elements and the development of bladder cancer using genome-wide association study (GWAS) summary statistics for 731 immune cell phenotypes and 91 circulating inflammatory factors (cases=2,053; controls=287,137). The primary analytical approach was Inverse Variance Weighting (IVW), supplemented by MR-Egger regression, weighted median, and weighted mode analyses. Sensitivity analyses included Cochran Q test, MR-Egger intercept test, and Leave-one-out test.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The findings indicated that monocytes are positively correlated with an increased risk of bladder cancer. On the contrary, double-negative (DN) T cells, HLA DR+CD8br, and CD28 on CD28+CD45RA+CD8br T cells exhibited an inverse correlation, suggesting a possible protective effect. Furthermore, inflammatory factors IL-20, IL-22RA1, and Eotaxin were significantly associated with an increased risk of bladder cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These results suggest that certain immune cell phenotypes and inflammatory factors may play a role in the development of bladder cancer and could serve as potential biomarkers for assessing tumor risk. The findings also offer new insights into the pathogenesis of bladder cancer, indicating a need for further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2024.1460275","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T07:58:05Z","timestamp":1728547085000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Understanding bladder cancer risk: Mendelian randomization analysis of immune cell and inflammatory factor influence"],"prefix":"10.3389","volume":"15","author":[{"given":"Hiocheng","family":"Un","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wumier","family":"Wusimanjiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renxuan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongren","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.eururo.2023.08.016","article-title":"European association of urology guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2023 guidelines","volume":"85","author":"Alfred Witjes","year":"2024","journal-title":"Eur Urol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/s41392-021-00658-5","article-title":"Inflammation and tumor progression: signaling pathways and targeted intervention","volume":"6","author":"Zhao","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"B4","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.immuni.2014.06.010","article-title":"Tumor-associated macrophages: from mechanisms to therapy","volume":"41","author":"Noy","year":"2014","journal-title":"Immunity"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.542492","article-title":"Dysregulation of the immune microenvironment contributes to Malignant progression and has prognostic value in bladder cancer","volume":"10","author":"Zheng","year":"2020","journal-title":"Front Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.03.003","article-title":"Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells","volume":"38","author":"Ma","year":"2013","journal-title":"Immunity"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-1248","article-title":"Single-cell sequencing reveals trajectory of tumor-infiltrating lymphocyte states in pancreatic cancer","volume":"12","author":"Schalck","year":"2022","journal-title":"Cancer Discov"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0437939100","article-title":"IL-1 is required for tumor invasiveness and angiogenesis","volume":"100","author":"Voronov","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39065","article-title":"The tumor-promoting actions of TNF-alpha involve TNFR1 and IL-17 in ovarian cancer in mice and humans","volume":"119","author":"Charles","year":"2009","journal-title":"J Clin Invest"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32247-X","article-title":"Effect of interleukin-1\u03b2 inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial","volume":"390","author":"Ridker","year":"2017","journal-title":"Lancet"},{"key":"B11","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1158\/1940-6207.CAPR-16-0209","article-title":"Targeting inflammation in cancer prevention and therapy","volume":"9","author":"Todoric","year":"2016","journal-title":"Cancer Prev Res (Phila)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s12865-024-00612-4","article-title":"Association of interleukin-17A and chemokine\/vascular endothelial growth factor-induced angiogenesis in newly diagnosed patients with bladder cancer","volume":"25","author":"Moadab","year":"2024","journal-title":"BMC Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.325.7378.1437","article-title":"Data dredging, bias, or confounding","volume":"325","author":"Smith","year":"2002","journal-title":"Bmj"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/sim.v27:8","article-title":"Mendelian randomization: using genes as instruments for making causal inferences in epidemiology","volume":"27","author":"Lawlor","year":"2008","journal-title":"Stat Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.18236","article-title":"Strengthening the reporting of observational studies in epidemiology using mendelian randomization: the STROBE-MR statement","volume":"326","author":"Skrivankova","year":"2021","journal-title":"Jama"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n2233","article-title":"Strengthening the reporting of observational studies in epidemiology using mendelian randomisation (STROBE-MR): explanation and elaboration","volume":"375","author":"Skrivankova","year":"2021","journal-title":"Bmj"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s40471-017-0128-6","article-title":"Recent developments in mendelian randomization studies","volume":"4","author":"Zheng","year":"2017","journal-title":"Curr Epidemiol Rep"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-0684-4","article-title":"Complex genetic signatures in immune cells underlie autoimmunity and inform therapy","volume":"52","author":"Orru","year":"2020","journal-title":"Nat Genet"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01588-w","article-title":"Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets","volume":"24","author":"Zhao","year":"2023","journal-title":"Nat Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1186\/s12888-023-05081-4","article-title":"Causal role of immune cells in schizophrenia: Mendelian randomization (MR) study","volume":"23","author":"Wang","year":"2023","journal-title":"BMC Psychiatry"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007081","article-title":"Orienting the causal relationship between imprecisely measured traits using GWAS summary data","volume":"13","author":"Hemani","year":"2017","journal-title":"PloS Genet"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.2013.37.issue-7","article-title":"Mendelian randomization analysis with multiple genetic variants using summarized data","volume":"37","author":"Burgess","year":"2013","journal-title":"Genet Epidemiol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-017-0276-5","article-title":"Erratum to: Interpreting findings from Mendelian randomization using the MR-Egger method","volume":"32","author":"Burgess","year":"2017","journal-title":"Eur J Epidemiol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.2016.40.issue-4","article-title":"Consistent estimation in mendelian randomization with some invalid instruments using a weighted median estimator","volume":"40","author":"Bowden","year":"2016","journal-title":"Genet Epidemiol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyx102","article-title":"Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption","volume":"46","author":"Hartwig","year":"2017","journal-title":"Int J Epidemiol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat Genet"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyy258","article-title":"Improving the accuracy of two-sample summary-data Mendelian randomization: moving beyond the NOME assumption","volume":"48","author":"Bowden","year":"2019","journal-title":"Int J Epidemiol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/s41392-023-01471-y","article-title":"T cells in health and disease","volume":"8","author":"Sun","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"B29","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3390\/cancers13246167","article-title":"Effector mechanisms of CD8+ HLA-DR+ T cells in breast cancer patients who respond to neoadjuvant chemotherapy","volume":"13","author":"Osuna-G\u00f3mez","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.13795","article-title":"Double-negative T cells inhibit proliferation and invasion of human pancreatic cancer cells in co-culture","volume":"39","author":"Lu","year":"2019","journal-title":"Anticancer Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-02-258558","article-title":"Nomenclature of monocytes and dendritic cells in blood","volume":"116","author":"Ziegler-Heitbrock","year":"2010","journal-title":"Blood"},{"key":"B32","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1146\/annurev-pathmechdis-012418-013058","article-title":"Monocytes in the tumor microenvironment","volume":"16","author":"Ugel","year":"2021","journal-title":"Annu Rev Pathol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2009.01.040","article-title":"Bladder tumor infiltrating mature dendritic cells and macrophages as predictors of response to bacillus calmette-gu\u00e9rin immunotherapy","volume":"55","author":"Ayari","year":"2009","journal-title":"Eur Urol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.v131.10","article-title":"Tumor-promoting macrophages induce the expression of the macrophage-specific receptor CD163 in Malignant cells","volume":"131","author":"Maniecki","year":"2012","journal-title":"Int J Cancer"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s13402-023-00820-x","article-title":"Single-cell RNA sequencing reveals the cellular and molecular characteristics of high-grade and metastatic bladder cancer","volume":"46","author":"Zheng","year":"2023","journal-title":"Cell Oncol (Dordr)"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01147","article-title":"The CD14(+)HLA-DR(lo\/neg) monocyte: an immunosuppressive phenotype that restrains responses to cancer immunotherapy","volume":"10","author":"Mengos","year":"2019","journal-title":"Front Immunol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1038\/nrc2734","article-title":"STATs in cancer inflammation and immunity: a leading role for STAT3","volume":"9","author":"Yu","year":"2009","journal-title":"Nat Rev Cancer"},{"key":"B38","doi-asserted-by":"publisher","first-page":"111077","DOI":"10.1016\/j.biopha.2020.111077","article-title":"Pre-clinical investigation of STAT3 pathway in bladder cancer: Paving the way for clinical translation","volume":"133","author":"Mirzaei","year":"2021","journal-title":"BioMed Pharmacother"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/nri3766","article-title":"The IL-20 subfamily of cytokines\u2013from host defence to tissue homeostasis","volume":"14","author":"Rutz","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.410233","article-title":"Interleukin-20 promotes migration of bladder cancer cells through extracellular signal-regulated kinase (ERK)-mediated MMP-9 protein expression leading to nuclear factor (NF-\u03baB) activation by inducing the up-regulation of p21(WAF1) protein expression","volume":"288","author":"Lee","year":"2013","journal-title":"J Biol Chem"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27189","article-title":"IL-20 and IL-20R1 antibodies protect against liver fibrosis","volume":"60","author":"Chiu","year":"2014","journal-title":"Hepatology"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102843","article-title":"Anti-IL-20 monoclonal antibody suppresses breast cancer progression and bone osteolysis in murine models","volume":"188","author":"Hsu","year":"2012","journal-title":"J Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0040267","article-title":"Identification of pro-inflammatory cytokines associated with muscle invasive bladder cancer; the roles of IL-5, IL-20, and IL-28A","volume":"7","author":"Lee","year":"2012","journal-title":"PloS One"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2021.05.010","article-title":"High IL-22RA1 gene expression is associated with poor outcome in muscle invasive bladder cancer","volume":"39","author":"Nitschke","year":"2021","journal-title":"Urol Oncol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.11.5397","article-title":"Cutting edge: immune cells as sources and targets of the IL-10 family members","volume":"168","author":"Wolk","year":"2002","journal-title":"J Immunol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/s41573-022-00557-6","article-title":"Emerging principles of cytokine pharmacology and therapeutics","volume":"22","author":"Saxton","year":"2023","journal-title":"Nat Rev Drug Discov"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1460275\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T07:58:09Z","timestamp":1728547089000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1460275\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,10]]},"references-count":46,"alternative-id":["10.3389\/fimmu.2024.1460275"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1460275","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,10]]},"article-number":"1460275"}}