{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:30:15Z","timestamp":1793039415592,"version":"4.5.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"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>Background<\/jats:title>\n                    <jats:p>Antigen processing and presentation (APP) is required for tumor immune recognition, but its relationship with the immune landscape in colorectal cancer (CRC) remains incompletely defined. In this study, APP-related transcriptional programs were used as the starting point to identify immune-cell-associated biomarkers with prognostic and immunotherapeutic relevance in CRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Six public CRC bulk cohorts were analyzed to define APP-related molecular states. Weighted gene co-expression network analysis and four machine-learning frameworks, including Boruta, LassoLR, Pamr, and XGBoost, were applied to prioritize genes linked to APP activity. Single-cell analysis was performed with an atlas of 121 samples and 169,427 cells to identify the cellular origin of the candidate gene. Immune infiltration, cancer-immunity-cycle activity, immune checkpoint blockade (ICB) response, predicted drug response, somatic mutation patterns, and\n                      <jats:italic>in vitro<\/jats:italic>\n                      function were then evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Two APP-associated patterns were identified and showed different survival outcomes and immune landscapes. Network- and machine-learning-based screening prioritized IL18BP as the main APP-associated candidate. Higher IL18BP expression was associated with longer survival and an immune-active phenotype, including stronger antigen-presentation signals, increased immune infiltration, checkpoint-related signatures, and cancer-immunity-cycle activation. Single-cell profiling showed that IL18BP was preferentially enriched in dendritic cells (DCs), linking the APP-derived bulk signature to a DC-centered immunoregulatory compartment. Across nine external ICB-treated cohorts, IL18BP showed response-classification performance. Drug-response prediction and somatic mutation analyses identified additional features associated with IL18BP-defined groups. In CRC cell lines, IL18BP knockdown increased proliferation, migration, and invasion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings identify IL18BP as a DC-enriched, APP-associated biomarker in CRC. By connecting APP programs in bulk tumors with DC-level expression patterns at single-cell resolution, this study positions IL18BP as an APP-associated marker of a DC-enriched immune state. These findings support further evaluation of IL18BP for prognostic and immunotherapy stratification in colorectal cancer but do not establish a causal APP-DC-IL18BP pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1973858","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:32:10Z","timestamp":1791178330000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["IL18BP links antigen processing and presentation programs to a dendritic cell-enriched immunoregulatory state in colorectal cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Junyin","family":"Zheng","sequence":"first","affiliation":[{"name":"Fuzhou University Affiliated Provincial Hospital, School of Medicine, Fuzhou University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guodong","family":"Guo","sequence":"additional","affiliation":[{"name":"Fuzhou University Affiliated Provincial Hospital, School of Medicine, Fuzhou University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Tian","sequence":"additional","affiliation":[{"name":"Fujian Medical University Union Hospital","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqi","family":"Chen","sequence":"additional","affiliation":[{"name":"Fuzhou University Affiliated Provincial Hospital, School of Medicine, Fuzhou University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyun","family":"Xia","sequence":"additional","affiliation":[{"name":"Fuzhou University Affiliated Provincial Hospital, School of Medicine, Fuzhou University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqing","family":"Jiang","sequence":"additional","affiliation":[{"name":"Fuzhou University Affiliated Provincial Hospital, School of Medicine, Fuzhou University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dajia","family":"Lin","sequence":"additional","affiliation":[{"name":"Fuzhou University Affiliated Provincial Hospital, School of Medicine, Fuzhou University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenshen","family":"Huang","sequence":"additional","affiliation":[{"name":"Fuzhou University Affiliated Provincial Hospital, School of Medicine, Fuzhou University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.12.003","article-title":"Tumor \"age\" in early-onset colorectal cancer","volume":"188","author":"Mauri","year":"2025","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-023-10158-3","article-title":"Colorectal cancer: a comprehensive review of carcinogenesis, diagnosis, and novel strategies for classified treatments","volume":"43","author":"Abedizadeh","year":"2024","journal-title":"Cancer Metastasis Rev"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1433315","article-title":"Immunotherapy for colorectal cancer","volume":"15","author":"Yu","year":"2024","journal-title":"Front Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00707-2","article-title":"A guide to antigen processing and presentation","volume":"22","author":"Pishesha","year":"2022","journal-title":"Nat Rev Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-023-00789-4","article-title":"Antigen presentation in cancer - mechanisms and clinical implications for immunotherapy","volume":"20","author":"Yang","year":"2023","journal-title":"Nat Rev Clin Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001111","article-title":"Antigen processing and presentation in cancer immunotherapy","volume":"8","author":"Lee","year":"2020","journal-title":"J Immunother Cancer"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-026-01330-1","article-title":"Interleukin-18 armours antitumour immune effectors","author":"Sharma","year":"2026","journal-title":"Nat Rev Immunol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"13505","DOI":"10.3390\/ijms252413505","article-title":"IL-18 and IL-18BP: A unique dyad in health and disease","volume":"25","author":"Novick","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/srep33273","article-title":"Evaluation of frozen tissue-derived prognostic gene expression signatures in FFPE colorectal cancer samples","volume":"6","author":"Zhu","year":"2016","journal-title":"Sci Rep"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.11.005","article-title":"Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer","volume":"138","author":"Smith","year":"2010","journal-title":"Gastroenterology"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s11605-011-1815-0","article-title":"Complementary strand microRNAs mediate acquisition of metastatic potential in colonic adenocarcinoma","volume":"16","author":"Chen","year":"2012","journal-title":"J Gastrointest Surg"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0902232106","article-title":"Association of survival and disease progression with chromosomal instability: a genomic exploration of colorectal cancer","volume":"106","author":"Sheffer","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"B13","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1038\/s41588-020-0636-z","article-title":"Lineage-dependent gene expression programs influence the immune landscape of colorectal cancer","volume":"52","author":"Lee","year":"2020","journal-title":"Nat Genet"},{"key":"B14","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/nbt.3192","article-title":"Spatial reconstruction of single-cell gene expression data","volume":"33","author":"Satija","year":"2015","journal-title":"Nat Biotechnol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq170","article-title":"ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking","volume":"26","author":"Wilkerson","year":"2010","journal-title":"Bioinformatics"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-559","article-title":"WGCNA: an R package for weighted correlation network analysis","volume":"9","author":"Langfelder","year":"2008","journal-title":"BMC Bioinf"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3233\/FI-2010-288","article-title":"Boruta \u2013 a system for feature selection","volume":"101","author":"Kursa","year":"2010","journal-title":"Fundam Inform"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1002\/bjs.10895","article-title":"LASSO regression","volume":"105","author":"Ranstam","year":"2018","journal-title":"J Br Surg"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.082099299","article-title":"Diagnosis of multiple cancer types by shrunken centroids of gene expression","volume":"99","author":"Tibshirani","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"B21","doi-asserted-by":"crossref","DOI":"10.1145\/2939672.2939785","article-title":"Xgboost: a scalable tree boosting system","author":"Chen","year":"2016"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2612","DOI":"10.1038\/ncomms3612","article-title":"Inferring tumour purity and stromal and immune cell admixture from expression data","volume":"4","author":"Yoshihara","year":"2013","journal-title":"Nat Commun"},{"key":"B23","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.cell.2014.12.033","article-title":"Molecular and genetic properties of tumors associated with local immune cytolytic activity","volume":"160","author":"Rooney","year":"2015","journal-title":"Cell"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1172\/JCI91190","article-title":"IFN-gamma-related mRNA profile predicts clinical response to PD-1 blockade","volume":"127","author":"Ayers","year":"2017","journal-title":"J Clin Invest"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aah3560","article-title":"Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance","volume":"9","author":"Roh","year":"2017","journal-title":"Sci Transl Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf8399","article-title":"Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy","volume":"355","author":"Davoli","year":"2017","journal-title":"Science"},{"key":"B27","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1016\/j.cell.2018.09.006","article-title":"A cancer cell program promotes T cell exclusion and resistance to checkpoint blockade","volume":"175","author":"Jerby-Arnon","year":"2018","journal-title":"Cell"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/smtd.202301685","article-title":"A predictive network-based immune checkpoint blockade immunotherapeutic signature optimizing patient selection and treatment strategies","volume":"8","author":"Zhang","year":"2024","journal-title":"Small Methods"},{"key":"B29","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1186\/s12943-024-02169-7","article-title":"Uncovering the predictive and immunomodulatory potential of transient receptor potential melastatin family-related CCNE1 in pan-cancer","volume":"23","author":"Zhang","year":"2024","journal-title":"Mol Cancer"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat Commun"},{"key":"B31","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1186\/s13059-016-1070-5","article-title":"Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression","volume":"17","author":"Becht","year":"2016","journal-title":"Genome Biol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.12.019","article-title":"Pan-cancer immunogenomic analyses reveal genotype-immunophenotype relationships and predictors of response to checkpoint blockade","volume":"18","author":"Charoentong","year":"2017","journal-title":"Cell Rep"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa407","article-title":"TIMER2.0 for analysis of tumor-infiltrating immune cells","volume":"48","author":"Li","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.immuni.2013.07.012","article-title":"Oncology meets immunology: the cancer-immunity cycle","volume":"39","author":"Chen","year":"2013","journal-title":"Immunity"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbab260","article-title":"oncoPredict: an R package for predicting in vivo or cancer patient drug response and biomarkers from cell line screening data","volume":"22","author":"Maeser","year":"2021","journal-title":"Brief Bioinform"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1101\/gr.239244.118","article-title":"Maftools: efficient and comprehensive analysis of somatic variants in cancer","volume":"28","author":"Mayakonda","year":"2018","journal-title":"Genome Res"},{"key":"B37","doi-asserted-by":"publisher","first-page":"134","DOI":"10.3390\/cancers13010134","article-title":"The role of antigen processing and presentation in cancer and the efficacy of immune checkpoint inhibitor immunotherapy","volume":"13","author":"Mpakali","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.3390\/biomedicines10071750","article-title":"Interleukin-18 binding protein in immune regulation and autoimmune diseases","volume":"10","author":"Park","year":"2022","journal-title":"Biomedicines"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1973858\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:32:11Z","timestamp":1791178331000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1973858\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":38,"alternative-id":["10.3389\/fimmu.2026.1973858"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1973858","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,5]]},"article-number":"1973858"}}