{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:31:55Z","timestamp":1787311915642,"version":"build-2736575974"},"reference-count":127,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"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>Diffuse gliomas are now diagnosed and studied through integrated molecular classification, radiomics, single-cell biology, spatial profiling, proteogenomics, metabolomics, and artificial intelligence. Yet many precision-medicine models still begin at diagnosis and emphasize tumor-intrinsic molecular features, leaving environmental, occupational, lifestyle, microbiome, metabolic, immune, and treatment-related exposures at the margins. This review develops an exposome-informed view of diffuse glioma biomarker discovery. Biomarker discovery is separated from clinical prevention: current evidence does not justify population-level glioma screening based on environmental exposures, but it does support systematic integration of external exposures and internal exposure-related molecular states with tumor and host biology. The synthesis focuses on five linked dimensions: the limits of current artificial intelligence and multi-omics models when exposure biology is excluded; glioma-relevant exposure domains stratified by evidence strength and measurability; genotoxic, epigenetic, vascular, neuroimmune, and immunometabolic conduits through which exposures may shape tumor ecology; computational strategies for temporally anchored integration of geospatial, occupational, clinical, liquid-biopsy, imaging, tumor-omic, single-cell, spatial, microbiome, and metabolomic data; and clinically realistic applications in high-risk surveillance, recurrence-aware monitoring, treatment-toxicity reduction, and biomarker-guided trial stratification. By aligning exposome science with systems neuro-oncology, the review outlines a translational agenda for exposure-aware glioma biomarkers while maintaining a conservative boundary between established evidence, mechanistic hypotheses, and future clinical implementation.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1874861","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T10:52:22Z","timestamp":1787309542000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exposure-aware multi-omics and artificial intelligence for biomarker discovery and precision prevention in diffuse glioma"],"prefix":"10.3389","volume":"17","author":[{"given":"Suming","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Radiology, Key Laboratory of Obstetric & Gynecologic and Pediatric Disease and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilin","family":"Si","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Suining First People\u2019s Hospital","place":["Suining, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Suining First People\u2019s Hospital","place":["Suining, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Suining First People\u2019s Hospital","place":["Suining, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"vi1","DOI":"10.1093\/neuonc\/noae145","article-title":"CBTRUS statistical report: Primary brain and other central nervous system tumors diagnosed in the United States in 2017-2021","volume":"26","author":"Price","year":"2024","journal-title":"Neuro Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.0023","article-title":"Glioblastoma and other primary brain Malignancies in adults: A review","volume":"329","author":"Schaff","year":"2023","journal-title":"JAMA"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO classification of tumors of the central nervous system: a summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-020-00447-z","article-title":"EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood","volume":"18","author":"Weller","year":"2021","journal-title":"Nat Rev Clin Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1056\/NEJMoa043331","article-title":"MGMT gene silencing and benefit from temozolomide in glioblastoma","volume":"352","author":"Hegi","year":"2005","journal-title":"N Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2020.02.010","article-title":"MGMT status as a clinical biomarker in glioblastoma","volume":"6","author":"Butler","year":"2020","journal-title":"Trends Cancer"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nature07385","article-title":"Comprehensive genomic characterization defines human glioblastoma genes and core pathways","volume":"455","year":"2008","journal-title":"Nature"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.09.034","article-title":"The somatic genomic landscape of glioblastoma","volume":"155","author":"Brennan","year":"2013","journal-title":"Cell"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.12.028","article-title":"Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma","volume":"164","author":"Ceccarelli","year":"2016","journal-title":"Cell"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1407279","article-title":"Glioma groups based on 1p\/19q, IDH, and TERT promoter mutations in tumors","volume":"372","author":"Eckel-Passow","year":"2015","journal-title":"N Engl J Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.08.024","article-title":"Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma","volume":"22","author":"Sturm","year":"2012","journal-title":"Cancer Cell"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/nature10866","article-title":"IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype","volume":"483","author":"Turcan","year":"2012","journal-title":"Nature"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02969-w","article-title":"A prognostic neural epigenetic signature in high-grade glioma","volume":"30","author":"Drexler","year":"2024","journal-title":"Nat Med"},{"key":"B15","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1016\/j.cell.2019.06.024","article-title":"An integrative model of cellular states, plasticity, and genetics for glioblastoma","volume":"178","author":"Neftel","year":"2019","journal-title":"Cell"},{"key":"B16","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/j.ccell.2021.01.006","article-title":"Proteogenomic and metabolomic characterization of human glioblastoma","volume":"39","author":"Wang","year":"2021","journal-title":"Cancer Cell"},{"key":"B17","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.ccell.2022.05.009","article-title":"Spatially resolved multi-omics deciphers bidirectional tumor-host interdependence in glioblastoma","volume":"40","author":"Ravi","year":"2022","journal-title":"Cancer Cell"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2485","DOI":"10.1016\/j.cell.2024.03.029","article-title":"Integrative spatial analysis reveals a multi-layered organization of glioblastoma","volume":"187","author":"Greenwald","year":"2024","journal-title":"Cell"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adn4306","article-title":"Single-cell multi-omics sequencing uncovers region-specific plasticity of glioblastoma for complementary therapeutic targeting","volume":"10","author":"Wang","year":"2024","journal-title":"Sci Adv"},{"key":"B20","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1007\/s12672-025-02431-4","article-title":"Integrating multi-omics data to identify the role of Aggrephagy-related genes in tumor microenvironment and key tumorigenesis factors of GB from the perspective of single-cell sequencing","volume":"16","author":"Chen","year":"2025","journal-title":"Discov Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-05-0456","article-title":"Complementing the genome with an \"exposome\": the outstanding challenge of environmental exposure measurement in molecular epidemiology","volume":"14","author":"Wild","year":"2005","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1126\/science.1192603","article-title":"Epidemiology. Environment and disease risks","volume":"330","author":"Rappaport","year":"2010","journal-title":"Science"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/em.21777","article-title":"Measuring the exposome: a powerful basis for evaluating environmental exposures and cancer risk","volume":"54","author":"Wild","year":"2013","journal-title":"Environ Mol Mutagen"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2020.105887","article-title":"What is new in the exposome","volume":"143","author":"Vineis","year":"2020","journal-title":"Environ Int"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010818-021315","article-title":"The exposome: Molecules to populations","volume":"59","author":"Niedzwiecki","year":"2019","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"97008","DOI":"10.1289\/EHP4713","article-title":"Generating the blood exposome database using a comprehensive text mining and database fusion approach","volume":"127","author":"Barupal","year":"2019","journal-title":"Environ Health Perspect"},{"key":"B27","doi-asserted-by":"publisher","first-page":"7024","DOI":"10.1038\/s41467-022-34422-2","article-title":"Multi-omics signatures of the human early life exposome","volume":"13","author":"Maitre","year":"2022","journal-title":"Nat Commun"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1101\/gr.276521.121","article-title":"Precision environmental health monitoring by longitudinal exposome and multi-omics profiling","volume":"32","author":"Gao","year":"2022","journal-title":"Genome Res"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2024.108930","article-title":"Integrating multi-omics with environmental data for precision health: A novel analytic framework and case study on prenatal mercury induced childhood fatty liver disease","volume":"190","author":"Goodrich","year":"2024","journal-title":"Environ Int"},{"key":"B30","doi-asserted-by":"publisher","first-page":"9362","DOI":"10.3390\/ijms26199362","article-title":"Artificial intelligence-driven multi-omics approaches in glioblastoma","volume":"26","author":"Morello","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B31","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1002\/acn3.70249","article-title":"Multi-omics integration for advancing glioma precision medicine","volume":"13","author":"Guarnaccia","year":"2026","journal-title":"Ann Clin Transl Neurol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"24874","DOI":"10.1038\/s41598-025-09742-0","article-title":"Comprehensive multi-omics and machine learning framework for glioma subtyping and precision therapeutics","volume":"15","author":"Ding","year":"2025","journal-title":"Sci Rep"},{"key":"B33","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s40644-024-00682-y","article-title":"Artificial intelligence-based MRI radiomics and radiogenomics in glioma","volume":"24","author":"Fan","year":"2024","journal-title":"Cancer Imaging"},{"key":"B34","doi-asserted-by":"publisher","first-page":"797","DOI":"10.3390\/diagnostics15070797","article-title":"Diagnostic accuracy of deep learning models in predicting glioma molecular markers: A systematic review and meta-analysis","volume":"15","author":"Farahani","year":"2025","journal-title":"Diagnostics (Basel)"},{"key":"B35","doi-asserted-by":"publisher","first-page":"545","DOI":"10.3390\/cancers15020545","article-title":"Multimodal deep learning-based prognostication in glioma patients: A systematic review","volume":"15","author":"Alleman","year":"2023","journal-title":"Cancers (Basel)"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.5152\/dir.2021.21153","article-title":"Diagnostic performance of radiomics using machine learning algorithms to predict MGMT promoter methylation status in glioma patients: a meta-analysis","volume":"27","author":"Huang","year":"2021","journal-title":"Diagn Interv Radiol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.crad.2022.08.138","article-title":"Glioma radiogenomics and artificial intelligence: road to precision cancer medicine","volume":"78","author":"Mahajan","year":"2023","journal-title":"Clin Radiol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-021-08400-z","article-title":"Artificial intelligence on MRI for molecular subtyping of diffuse gliomas: feature comparison, visualization, and correlation between radiomics and deep learning","volume":"32","author":"Zhou","year":"2022","journal-title":"Eur Radiol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2021.04.043","article-title":"Machine learning applications to neuroimaging for glioma detection and classification: An artificial intelligence augmented systematic review","volume":"89","author":"Buchlak","year":"2021","journal-title":"J Clin Neurosci"},{"key":"B40","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1093\/neuonc\/noaa163","article-title":"Artificial intelligence neuropathologist for glioma classification using deep learning on hematoxylin and eosin stained slide images and molecular markers","volume":"23","author":"Jin","year":"2021","journal-title":"Neuro Oncol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.35441","article-title":"A strategy for multimodal integration of transcriptomics, proteomics, and radiomics data for the prediction of recurrence in patients with IDH-mutant gliomas","volume":"157","author":"Chouleur","year":"2025","journal-title":"Int J Cancer"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1090040","article-title":"Identification and validation of neurotrophic factor-related gene signatures in glioblastoma and Parkinson's disease","volume":"14","author":"Zhao","year":"2023","journal-title":"Front Immunol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/s43018-022-00510-x","article-title":"Integrative multi-omics networks identify PKC\u03b4 and DNA-PK as master kinases of glioblastoma subtypes and guide targeted cancer therapy","volume":"4","author":"Migliozzi","year":"2023","journal-title":"Nat Cancer"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2023.216380","article-title":"Noninvasive radiomics model reveals macrophage infiltration in glioma","volume":"573","author":"Fan","year":"2023","journal-title":"Cancer Lett"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.02.009","article-title":"The microenvironmental landscape of brain tumors","volume":"31","author":"Quail","year":"2017","journal-title":"Cancer Cell"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1016\/j.cell.2020.05.007","article-title":"Interrogation of the microenvironmental landscape in brain tumors reveals disease-specific alterations of immune cells","volume":"181","author":"Klemm","year":"2020","journal-title":"Cell"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1016\/j.cell.2020.04.055","article-title":"Single-cell mapping of human brain cancer reveals tumor-specific instruction of tissue-invading leukocytes","volume":"181","author":"Friebel","year":"2020","journal-title":"Cell"},{"key":"B48","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1038\/s41467-022-28372-y","article-title":"Single-cell analysis of human glioma and immune cells identifies S100A4 as an immunotherapy target","volume":"13","author":"Abdelfattah","year":"2022","journal-title":"Nat Commun"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1038\/s41467-021-21407-w","article-title":"Single-cell RNA sequencing reveals functional heterogeneity of glioma-associated brain macrophages","volume":"12","author":"Ochocka","year":"2021","journal-title":"Nat Commun"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1172\/JCI163446","article-title":"Macrophages and microglia in glioblastoma: heterogeneity, plasticity, and therapy","volume":"133","author":"Khan","year":"2023","journal-title":"J Clin Invest"},{"key":"B51","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1016\/j.ccell.2024.03.013","article-title":"Identification of hypoxic macrophages in glioblastoma with therapeutic potential for vasculature normalization","volume":"42","author":"Wang","year":"2024","journal-title":"Cancer Cell"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.1016\/j.immuni.2023.06.017","article-title":"Hypoxic niches attract and sequester tumor-associated macrophages and cytotoxic T cells and reprogram them for immunosuppression","volume":"56","author":"Sattiraju","year":"2023","journal-title":"Immunity"},{"key":"B53","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1158\/2159-8290.CD-22-0455","article-title":"Targeting microglial metabolic rewiring synergizes with immune-checkpoint blockade therapy for glioblastoma","volume":"13","author":"Ye","year":"2023","journal-title":"Cancer Discov"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-24-3362","article-title":"Lipid-laden macrophages recycle myelin to feed glioblastoma","volume":"84","author":"Pang","year":"2024","journal-title":"Cancer Res"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1172\/JCI141083","article-title":"SLIT2\/ROBO signaling in tumor-associated microglia and macrophages drives glioblastoma immunosuppression and vascular dysmorphia","volume":"131","author":"Geraldo","year":"2021","journal-title":"J Clin Invest"},{"key":"B56","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/s13073-021-00906-x","article-title":"Single-cell characterization of macrophages in glioblastoma reveals MARCO as a mesenchymal pro-tumor marker","volume":"13","author":"Chen","year":"2021","journal-title":"Genome Med"},{"key":"B57","doi-asserted-by":"publisher","first-page":"5041","DOI":"10.3390\/cancers14205041","article-title":"Metabolomic and lipidomic profiling of gliomas-a new direction in personalized therapies","volume":"14","author":"Gaca-Tabaszewska","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B58","doi-asserted-by":"publisher","first-page":"478","DOI":"10.3390\/metabo10120478","article-title":"Metabolic alterations related to glioma grading based on metabolomics and lipidomics analyses","volume":"10","author":"Yu","year":"2020","journal-title":"Metabolites"},{"key":"B59","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1093\/neuonc\/noad208","article-title":"Proteometabolomics of initial and recurrent glioblastoma highlights an increased immune cell signature with altered lipid metabolism","volume":"26","author":"Cosenza-Contreras","year":"2024","journal-title":"Neuro Oncol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1186\/s40478-024-01861-5","article-title":"Metabolic remodeling in glioblastoma: a longitudinal multi-omics study","volume":"12","author":"Fontanilles","year":"2024","journal-title":"Acta Neuropathol Commun"},{"key":"B61","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1186\/s13046-025-03497-2","article-title":"Glioblastoma metabolomics: uncovering biomarkers for diagnosis, prognosis and targeted therapy","volume":"44","author":"Costantini","year":"2025","journal-title":"J Exp Clin Cancer Res"},{"key":"B62","doi-asserted-by":"publisher","first-page":"348","DOI":"10.3390\/ijms24010348","article-title":"Preclinical and clinical applications of metabolomics and proteomics in glioblastoma research","volume":"24","author":"Ahmed","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-51652-9_18","article-title":"Metabolomics of glioma","volume":"1280","author":"Feng","year":"2021","journal-title":"Adv Exp Med Biol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0882-3","article-title":"Tracking tumour evolution in glioma through liquid biopsies of cerebrospinal fluid","volume":"565","author":"Miller","year":"2019","journal-title":"Nature"},{"key":"B65","doi-asserted-by":"publisher","first-page":"658","DOI":"10.3390\/biom15050658","article-title":"Liquid biopsy-derived tumor biomarkers for clinical applications in glioblastoma","volume":"15","author":"de Lima","year":"2025","journal-title":"Biomolecules"},{"key":"B66","doi-asserted-by":"publisher","first-page":"7974","DOI":"10.3390\/ijms25147974","article-title":"Circulating liquid biopsy biomarkers in glioblastoma: advances and challenges","volume":"25","author":"Seyhan","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-024-01517-6","article-title":"Cerebrospinal fluid liquid biopsies in the evaluation of adult gliomas","volume":"26","author":"Valerius","year":"2024","journal-title":"Curr Oncol Rep"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noae068","article-title":"Circulating extracellular vesicles as biomarker for diagnosis, prognosis, and monitoring in glioblastoma patients","volume":"26","author":"Ricklefs","year":"2024","journal-title":"Neuro Oncol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1800","article-title":"Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers","volume":"10","author":"Skog","year":"2008","journal-title":"Nat Cell Biol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nou207","article-title":"Circulating glioma biomarkers","volume":"17","author":"Kros","year":"2015","journal-title":"Neuro Oncol"},{"key":"B71","doi-asserted-by":"publisher","first-page":"7074","DOI":"10.1038\/s41467-024-51332-7","article-title":"Clinical utility of a blood based assay for the detection of IDH1.R132H-mutant gliomas","volume":"15","author":"Batool","year":"2024","journal-title":"Nat Commun"},{"key":"B72","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1093\/neuonc\/nou087","article-title":"The epidemiology of glioma in adults: a \"state of the science\" review","volume":"16","author":"Ostrom","year":"2014","journal-title":"Neuro Oncol"},{"key":"B73","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-319-12048-5_1","article-title":"Epidemiology of gliomas","volume":"163","author":"Ostrom","year":"2015","journal-title":"Cancer Treat Res"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2019.08.004","article-title":"Environmental risk factors of primary brain tumors: a review","volume":"175","author":"Vienne-Jumeau","year":"2019","journal-title":"Rev Neurol (Paris)"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nos208","article-title":"Ionizing radiation and the risk of brain and central nervous system tumors: a systematic review","volume":"14","author":"Braganza","year":"2012","journal-title":"Neuro Oncol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevOncog.2018025740","article-title":"Radiation-induced gliomas","volume":"23","author":"Aherne","year":"2018","journal-title":"Crit Rev Oncog"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1093\/noajnl\/vdab109","article-title":"Defining the molecular features of radiation-induced glioma: a systematic review and meta-analysis","volume":"3","author":"Whitehouse","year":"2021","journal-title":"Neuro-Oncol Adv"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1093\/jncics\/pkz107","article-title":"Association between outdoor air pollution and risk of Malignant and benign brain tumors: the multiethnic cohort study","volume":"4","author":"Wu","year":"2020","journal-title":"JNCI Cancer Spectr"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000213920","article-title":"Ambient outdoor air pollution and risk of tumors of the central nervous system","volume":"105","author":"Hvidtfeldt","year":"2025","journal-title":"Neurology"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1007\/s10552-016-0721-x","article-title":"Air pollution from traffic and risk for brain tumors: a nationwide study in Denmark","volume":"27","author":"Poulsen","year":"2016","journal-title":"Cancer Causes Control"},{"key":"B81","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/s00401-005-0991-y","article-title":"Epidemiology and etiology of gliomas","volume":"109","author":"Ohgaki","year":"2005","journal-title":"Acta Neuropathol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1007\/s10552-021-01429-x","article-title":"Occupational exposure to pesticides and central nervous system tumors: results from the CERENAT case-control study","volume":"32","author":"Baldi","year":"2021","journal-title":"Cancer Causes Control"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwac007","article-title":"Pesticide residue intake from fruit and vegetable consumption and risk of glioma","volume":"191","author":"Cote","year":"2022","journal-title":"Am J Epidemiol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.834258","article-title":"Dietary factors and risk of glioma in adults: a systematic review and dose-response meta-analysis of observational studies","volume":"9","author":"Zhang","year":"2022","journal-title":"Front Nutr"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noz013","article-title":"Diet and risk of glioma: combined analysis of 3 large prospective studies in the UK and USA","volume":"21","author":"Kuan","year":"2019","journal-title":"Neuro Oncol"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1007\/s10143-023-02051-y","article-title":"Modifiable risk factors for glioblastoma: a systematic review and meta-analysis","volume":"46","author":"Yoshikawa","year":"2023","journal-title":"Neurosurg Rev"},{"key":"B87","doi-asserted-by":"publisher","first-page":"582","DOI":"10.3390\/nu17030582","article-title":"Latent association between diets and glioma risk: a Mendelian randomization analysis","volume":"17","author":"Zhao","year":"2025","journal-title":"Nutrients"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-15-0847","article-title":"Approaching a scientific consensus on the association between allergies and glioma risk: a report from the Glioma International Case-Control Study","volume":"25","author":"Amirian","year":"2016","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2022.878233","article-title":"Oral contraceptive and glioma risk: a prospective cohort study and meta-analysis","volume":"10","author":"Shao","year":"2022","journal-title":"Front Public Health"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2024.108983","article-title":"The effect of exposure to radiofrequency fields on cancer risk in the general and working population: a systematic review of human observational studies - part I: most researched outcomes","volume":"191","author":"Karipidis","year":"2024","journal-title":"Environ Int"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2024.108552","article-title":"Mobile phone use and brain tumour risk - COSMOS, a prospective cohort study","volume":"185","author":"Feychting","year":"2024","journal-title":"Environ Int"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2022.107487","article-title":"Time trends in mobile phone use and glioma incidence among males in the Nordic Countries, 1979-2016","volume":"168","author":"Deltour","year":"2022","journal-title":"Environ Int"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2023.102510","article-title":"Risk factors for childhood brain tumours: a systematic review and meta-analysis of observational studies from 1976 to 2022","volume":"88","author":"Onyije","year":"2024","journal-title":"Cancer Epidemiol"},{"key":"B94","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.3390\/biomedicines9101351","article-title":"Is the exposome involved in brain disorders through the serotoninergic system","volume":"9","author":"Sarrouilhe","year":"2021","journal-title":"Biomedicines"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1155\/mi\/2385129","article-title":"Integrative multi-omics identifies S100A4 as a translational hub linking environmental bis(2-ethylhexyl) phthalate (DEHP) exposure to glioblastoma risk","volume":"2026","author":"Tan","year":"2026","journal-title":"Mediators Inflammation"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2025.119155","article-title":"Deciphering the carcinogenic role of benzo[a]pyrene in glioblastoma: insights from network toxicology, single-cell transcriptomics, and Mendelian randomization","volume":"304","author":"Yi","year":"2025","journal-title":"Ecotoxicol Environ Saf"},{"key":"B97","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1007\/s12031-025-02354-3","article-title":"Causal association between sleep deprivation and glioblastoma risk: insights from multi-omics analysis","volume":"75","author":"Du","year":"2025","journal-title":"J Mol Neurosci"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1177\/09603271241241796","article-title":"Risk factors for glioblastoma are shared by other brain tumor types","volume":"43","author":"Smith","year":"2024","journal-title":"Hum Exp Toxicol"},{"key":"B99","doi-asserted-by":"publisher","first-page":"872","DOI":"10.18632\/aging.205426","article-title":"XRCC1: a potential prognostic and immunological biomarker in LGG based on systematic pan-cancer analysis","volume":"16","author":"Wang","year":"2024","journal-title":"Aging (Albany NY)"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1126\/science.aai8478","article-title":"Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq","volume":"355","author":"Venteicher","year":"2017","journal-title":"Science"},{"key":"B101","doi-asserted-by":"publisher","first-page":"3143","DOI":"10.1016\/j.neuron.2025.07.001","article-title":"Human brain vascular multi-omics elucidates disease-risk associations","volume":"113","author":"Reid","year":"2025","journal-title":"Neuron"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1527428","article-title":"Editorial: Immune cell exhaustion: new challenges and opportunities in cancer therapy","volume":"15","author":"Chi","year":"2024","journal-title":"Front Immunol"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1126\/science.abm5214","article-title":"Distinct myeloid-derived suppressor cell populations in human glioblastoma","volume":"387","author":"Jackson","year":"2025","journal-title":"Science"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-08633-8","article-title":"Programs, origins and immunomodulatory functions of myeloid cells in glioma","volume":"640","author":"Miller","year":"2025","journal-title":"Nature"},{"key":"B105","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1016\/j.immuni.2025.09.018","article-title":"Spatial immune profiling defines a subset of human gliomas with functional tertiary lymphoid structures","volume":"58","author":"Cakmak","year":"2025","journal-title":"Immunity"},{"key":"B106","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1038\/s41467-022-28523-1","article-title":"T-cell dysfunction in the glioblastoma microenvironment is mediated by myeloid cells releasing interleukin-10","volume":"13","author":"Ravi","year":"2022","journal-title":"Nat Commun"},{"key":"B107","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.immuni.2024.11.026","article-title":"Antigen presentation by tumor-associated macrophages drives T cells from a progenitor exhaustion state to terminal exhaustion","volume":"58","author":"Waibl Polania","year":"2025","journal-title":"Immunity"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05680-3","article-title":"Single-cell spatial immune landscapes of primary and metastatic brain tumours","volume":"614","author":"Karimi","year":"2023","journal-title":"Nature"},{"key":"B109","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.cell.2023.11.032","article-title":"Time-resolved single-cell transcriptomics defines immune trajectories in glioblastoma","volume":"187","author":"Kirschenbaum","year":"2024","journal-title":"Cell"},{"key":"B110","doi-asserted-by":"publisher","first-page":"2669","DOI":"10.1016\/j.immuni.2024.09.007","article-title":"Microglia and monocyte-derived macrophages drive progression of pediatric high-grade gliomas and are transcriptionally shaped by histone mutations","volume":"57","author":"Ross","year":"2024","journal-title":"Immunity"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-0400","article-title":"Circadian regulator CLOCK recruits immune-suppressive microglia into the GBM tumor microenvironment","volume":"10","author":"Chen","year":"2020","journal-title":"Cancer Discov"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1002\/imt2.70070","article-title":"The microbiome in cancer","volume":"4","author":"Lin","year":"2025","journal-title":"iMeta"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1128\/msystems.00457-24","article-title":"Multi-omics analysis reveals the interplay between intratumoral bacteria and glioma","volume":"10","author":"Li","year":"2025","journal-title":"mSystems"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1403316","article-title":"Dissecting causal relationships between gut microbiota, blood metabolites, and glioblastoma multiforme: a two-sample Mendelian randomization study","volume":"15","author":"Chen","year":"2024","journal-title":"Front Microbiol"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1002\/adbi.202000029","article-title":"Liquid biopsy strategies to distinguish progression from pseudoprogression and radiation necrosis in glioblastomas","volume":"4","author":"Yekula","year":"2020","journal-title":"Adv Biosyst"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2022.101167","article-title":"Extracellular vesicles in the glioblastoma microenvironment: a diagnostic and therapeutic perspective","volume":"91","author":"Russo","year":"2023","journal-title":"Mol Aspects Med"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.15252\/msb.20178124","article-title":"Multi-Omics Factor Analysis-a framework for unsupervised integration of multi-omics data sets","volume":"14","author":"Argelaguet","year":"2018","journal-title":"Mol Syst Biol"},{"key":"B118","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1186\/s13059-020-02015-1","article-title":"MOFA+: a statistical framework for comprehensive integration of multi-modal single-cell data","volume":"21","author":"Argelaguet","year":"2020","journal-title":"Genome Biol"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz667","article-title":"A latent unknown clustering integrating multi-omics data (LUCID) with phenotypic traits","volume":"36","author":"Peng","year":"2020","journal-title":"Bioinformatics"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2023.100561","article-title":"Multi-Omics profiling for health","volume":"22","author":"Babu","year":"2023","journal-title":"Mol Cell Proteomics"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.4251\/wjgo.v18.i1.114708","article-title":"Revisiting multi-region 16S sequencing in gastric cancer","volume":"18","author":"Luo","year":"2026","journal-title":"World J Gastrointest Oncol"},{"key":"B122","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s13073-023-01207-1","article-title":"Spatially resolved transcriptomic profiles reveal unique defining molecular features of infiltrative 5ALA-metabolizing cells associated with glioblastoma recurrence","volume":"15","author":"Andrieux","year":"2023","journal-title":"Genome Med"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1561388","article-title":"Single-cell and spatial transcriptomic insights into glioma cellular heterogeneity and metabolic adaptations","volume":"16","author":"Fu","year":"2025","journal-title":"Front Immunol"},{"key":"B124","doi-asserted-by":"publisher","first-page":"3412","DOI":"10.1038\/s41467-025-58252-0","article-title":"Plasma-to-tumour tissue integrated proteomics using nano-omics for biomarker discovery in glioblastoma","volume":"16","author":"Liu","year":"2025","journal-title":"Nat Commun"},{"key":"B125","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s11060-020-03483-y","article-title":"Immune suppression in gliomas","volume":"151","author":"Grabowski","year":"2021","journal-title":"J Neuro-Oncol"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-042524-025950","article-title":"Immunopathology of glioblastoma","volume":"21","author":"Li","year":"2026","journal-title":"Annu Rev Pathol"},{"key":"B127","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/s41392-025-02521-3","article-title":"When vaccines reset tumors: SARS-CoV-2 mRNA shots create a transient checkpoint-sensitive state","volume":"10","author":"Chi","year":"2025","journal-title":"Signal Transduct Target Ther"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1874861\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T10:52:23Z","timestamp":1787309543000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1874861\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":127,"alternative-id":["10.3389\/fimmu.2026.1874861"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1874861","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,21]]},"article-number":"1874861"}}