{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T15:31:25Z","timestamp":1782487885933,"version":"3.54.5"},"reference-count":258,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Inflammatory bowel diseases (IBD), encompassing ulcerative colitis and Crohn\u2019s disease, are associated with an increased risk of colorectal cancer through mechanisms driven by persistent mucosal inflammation. Chronic inflammatory signaling, recurrent epithelial injury, and altered tissue repair processes progressively reshape the intestinal microenvironment, promoting genomic instability and facilitating the development of colitis-associated colorectal cancer (CAC). Despite the well-established link between inflammation and tumorigenesis, only a subset of patients with long-standing IBD develops malignancy, highlighting the complexity of the regulatory effects of the ongoing inflammation on the tumor initiation and progression. This review discusses the multifaceted roles of innate and adaptive immune responses in CAC pathogenesis. Innate immune signaling mediated by pattern recognition receptors, particularly Toll-like receptors, integrates microbial and damage-associated signals to activate inflammatory pathways that regulate epithelial proliferation, survival, and tumor-promoting cytokine networks. Tumor-associated macrophages, neutrophils, and myeloid-derived suppressor cells contribute to carcinogenesis by sustaining chronic inflammation, promoting immunosuppression, and remodeling the tumor microenvironment, although under specific conditions these cells can also support antitumor immunity. Innate lymphocyte subsets participate in immune surveillance and epithelial homeostasis, yet may also amplify inflammatory circuits that influence tumor development. Adaptive immune populations further shape CAC evolution, as CD4+ T-helper subsets, CD8+ cytotoxic T lymphocytes, regulatory T cells, and B cells exert divergent effects depending on cytokine milieu, immune context, and disease stage. Understanding immune-cell plasticity and the molecular pathways governing these processes may facilitate the identification of predictive biomarkers and the development of targeted immunomodulatory strategies aimed at preventing CAC.<\/jats:p>","DOI":"10.3390\/cancers18081230","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T14:10:48Z","timestamp":1776089448000},"page":"1230","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Immunologic Drivers and Restraints in Colitis-Associated Colorectal Cancer"],"prefix":"10.3390","volume":"18","author":[{"given":"Rachele","family":"Frascatani","sequence":"first","affiliation":[{"name":"Department of Systems Medicine, University of \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7380-0269","authenticated-orcid":false,"given":"Federica","family":"Laudisi","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, University of \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6354-2443","authenticated-orcid":false,"given":"Carmine","family":"Stolfi","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, University of \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1339-9076","authenticated-orcid":false,"given":"Giovanni","family":"Monteleone","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, University of \u201cTor Vergata\u201d, 00133 Rome, Italy"},{"name":"Gastroenterology Unit, Policlinico Universitario Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1007\/s11739-023-03320-w","article-title":"Gut Inflammation and Tumorigenesis: Every Site Has a Different Tale to Tell","volume":"18","author":"Vanoli","year":"2023","journal-title":"Intern. Emerg. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/s41577-024-01008-6","article-title":"Strategies for Targeting Cytokines in Inflammatory Bowel Disease","volume":"24","author":"Neurath","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Triantaphyllopoulos, K.A., Ragia, N.D., Panagiotopoulou, M.-C.E., and Sourlingas, T.G. (2025). Integrating Inflammatory and Epigenetic Signatures in IBD-Associated Colorectal Carcinogenesis: Models, Mechanisms, and Clinical Implications. Int. J. Mol. Sci., 26.","DOI":"10.20944\/preprints202508.1820.v1"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ganesh, N., Grady, W.M., and Kaz, A.M. (2026). Epigenetic Alterations in Colitis-Associated Colorectal Cancer. Epigenomes, 10.","DOI":"10.3390\/epigenomes10010004"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1053\/j.gastro.2021.04.042","article-title":"Genetic and Epigenetic Characteristics of Inflammatory Bowel Disease\u2013Associated Colorectal Cancer","volume":"161","author":"Taira","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1053\/j.gastro.2021.05.063","article-title":"AGA Clinical Practice Update on Endoscopic Surveillance and Management of Colorectal Dysplasia in Inflammatory Bowel Diseases: Expert Review","volume":"161","author":"Murthy","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"27","DOI":"10.21037\/tgh-23-36","article-title":"From Random to Precise: Updated Colon Cancer Screening and Surveillance for Inflammatory Bowel Disease","volume":"9","author":"Fatakhova","year":"2024","journal-title":"Transl. Gastroenterol. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1053\/j.gastro.2020.12.036","article-title":"Prognostic Factors for Advanced Colorectal Neoplasia in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis","volume":"160","author":"Wijnands","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hirai, M., Kanatani, Y., Ueda, T., Sano, M., Arai, H., Miyake, Y., Tomita, N., Nemoto, S., and Suzuki, H. (2025). Analysis of Risk Factors for Colorectal Cancer Associated with Ulcerative Colitis Using Machine Learning: A Retrospective Longitudinal Study Using a National Database in Japan. Cancers, 17.","DOI":"10.3390\/cancers17233752"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"jjaf207","DOI":"10.1093\/ecco-jcc\/jjaf207","article-title":"Background Mucosal Inflammation Affects Colorectal Cancer Prognosis in Ulcerative Colitis: A Nationwide, Multicenter Study","volume":"20","author":"Ikebata","year":"2026","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"jjaf219","DOI":"10.1093\/ecco-jcc\/jjaf219","article-title":"Cumulative Incidence and Risk Factors for Advanced Neoplasia Following Inflammatory Bowel Disease-Related Low-Grade Dysplasia: A Danish Nationwide Cohort Study","volume":"19","author":"Andersen","year":"2025","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sato, Y., Tsujinaka, S., Miura, T., Kitamura, Y., Suzuki, H., and Shibata, C. (2023). Inflammatory Bowel Disease and Colorectal Cancer: Epidemiology, Etiology, Surveillance, and Management. Cancers, 15.","DOI":"10.3390\/cancers15164154"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9872","DOI":"10.3748\/wjg.v20.i29.9872","article-title":"Colorectal Cancer in Inflammatory Bowel Disease: The Risk, Pathogenesis, Prevention and Diagnosis","volume":"20","author":"Kim","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"De Cristofaro, E., Lolli, E., Migliozzi, S., Sincovih, S., Marafini, I., Zorzi, F., Troncone, E., Neri, B., Biancone, L., and Del Vecchio Blanco, G. (2023). Frequency and Predictors of Dysplasia in Pseudopolyp-like Colorectal Lesions in Patients with Long-Standing Inflammatory Bowel Disease. Cancers, 15.","DOI":"10.3390\/cancers15133361"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"jjae115","DOI":"10.1093\/ecco-jcc\/jjae115","article-title":"Preventable Predictive Factors of Post-Colonoscopy Colorectal Cancer in Inflammatory Bowel Disease","volume":"19","author":"Marafini","year":"2025","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"E1414","DOI":"10.1055\/a-1165-0169","article-title":"Modified Kudo Classification Can Improve Accuracy of Virtual Chromoendoscopy with FICE in Endoscopic Surveillance of Ulcerative Colitis","volume":"08","author":"Cassinotti","year":"2020","journal-title":"Endosc. Int. Open"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"jjaf196","DOI":"10.1093\/ecco-jcc\/jjaf196","article-title":"Frequency of Dysplasia in Endoscopically Resected Pseudopolyps in Inflammatory Bowel Diseases","volume":"19","author":"Marafini","year":"2025","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1038\/ajg.2015.65","article-title":"Forty-Year Analysis of Colonoscopic Surveillance Program for Neoplasia in Ulcerative Colitis: An Updated Overview","volume":"110","author":"Choi","year":"2015","journal-title":"Am. J. Gastroenterol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S2468-1253(17)30004-3","article-title":"Risk of Colorectal Cancer in Asian Patients with Ulcerative Colitis: A Systematic Review and Meta-Analysis","volume":"2","author":"Bopanna","year":"2017","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s10147-026-02970-y","article-title":"Statistics and Epidemiology of Inflammatory Bowel Disease-Associated Colorectal Neoplasia","volume":"31","author":"Shinagawa","year":"2026","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.cgh.2019.07.016","article-title":"Global Prevalence of Colorectal Neoplasia: A Systematic Review and Meta-Analysis","volume":"18","author":"Wong","year":"2020","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.dld.2023.10.001","article-title":"Dysplasia Detection Rates under a Surveillance Program in a Tertiary Referral Center for Inflammatory Bowel Diseases: Real-World Data","volume":"56","author":"Snir","year":"2024","journal-title":"Dig. Liver Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"17972","DOI":"10.3390\/ijms140917972","article-title":"Mechanisms of Action of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Mesalazine in the Chemoprevention of Colorectal Cancer","volume":"14","author":"Stolfi","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.14309\/ajg.0000000000002149","article-title":"Effect of Biologics on the Risk of Advanced-Stage Inflammatory Bowel Disease-Associated Intestinal Cancer: A Nationwide Study","volume":"118","author":"Seishima","year":"2023","journal-title":"Am. J. Gastroenterol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.bcp.2007.09.020","article-title":"Cyclooxygenase-2-Dependent and -Independent Inhibition of Proliferation of Colon Cancer Cells by 5-Aminosalicylic Acid","volume":"75","author":"Stolfi","year":"2008","journal-title":"Biochem. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Yalchin, M., Baker, A.-M., Graham, T.A., and Hart, A. (2021). Predicting Colorectal Cancer Occurrence in IBD. Cancers, 13.","DOI":"10.3390\/cancers13122908"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1097\/MIB.0b013e31828029c0","article-title":"Declining Risk of Colorectal Cancer in Inflammatory Bowel Disease: An Updated Meta-Analysis of Population-Based Cohort Studies","volume":"19","author":"Lutgens","year":"2013","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2724","DOI":"10.1111\/j.1572-0241.2005.00287.x","article-title":"Increased Risk of Intestinal Cancer in Crohn\u2019s Disease: A Meta-Analysis of Population-Based Cohort Studies","volume":"100","author":"Jess","year":"2005","journal-title":"Am. J. Gastroenterol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1007\/s00384-020-03635-6","article-title":"The Impact of COVID-19 Pandemic in the Colorectal Cancer Prevention","volume":"35","author":"Calabrese","year":"2020","journal-title":"Int. J. Color. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e255","DOI":"10.1016\/S2665-9913(20)30092-8","article-title":"Preventing COVID-19-Induced Pneumonia with Anticytokine Therapy","volume":"2","author":"Monteleone","year":"2020","journal-title":"Lancet Rheumatol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Monteleone, G., Calisi, C., Salvatori, S., and Marafini, I. (2025). Fundamental and Emerging Insights into Innate and Adaptive Immunity in Inflammatory Bowel Diseases. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1665530"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature01322","article-title":"Inflammation and Cancer","volume":"420","author":"Coussens","year":"2002","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nature07205","article-title":"Cancer-Related Inflammation","volume":"454","author":"Mantovani","year":"2008","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Deng, Y., Jia, X., Liu, L., He, Q., and Liu, L. (2025). The Role of Intestinal Macrophage Polarization in Colitis-Associated Colon Cancer. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1537631"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"115274","DOI":"10.1016\/j.intimp.2025.115274","article-title":"Multifaceted Role of Myeloid-Derived Suppressor Cells in Colorectal Cancer","volume":"163","author":"Zhang","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Fantini, M.C., Favale, A., Onali, S., and Facciotti, F. (2020). Tumor Infiltrating Regulatory T Cells in Sporadic and Colitis-Associated Colorectal Cancer: The Red Little Riding Hood and the Wolf. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186744"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1158\/2326-6066.CIR-17-0036","article-title":"Protumor Steering of Cancer Inflammation by P50 NF-\u03baB Enhances Colorectal Cancer Progression","volume":"6","author":"Porta","year":"2018","journal-title":"Cancer Immunol. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/s41590-024-02074-7","article-title":"Short IL-18 Generated by Caspase-3 Cleavage Mobilizes NK Cells to Suppress Tumor Growth","volume":"26","author":"Shen","year":"2025","journal-title":"Nat. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"149185","DOI":"10.1155\/2014\/149185","article-title":"Chronic Inflammation and Cytokines in the Tumor Microenvironment","volume":"2014","author":"Landskron","year":"2014","journal-title":"J. Immunol. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"11071","DOI":"10.3390\/ijms130911071","article-title":"The Dual Role of Inflammation in Colon Carcinogenesis","volume":"13","author":"Monteleone","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.it.2008.02.008","article-title":"Interleukin-21: A Critical Regulator of the Balance between Effector and Regulatory T-Cell Responses","volume":"29","author":"Monteleone","year":"2008","journal-title":"Trends Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1042\/CS20150132","article-title":"Interleukin-34 Sustains Inflammatory Pathways in the Gut","volume":"129","author":"Monteleone","year":"2015","journal-title":"Clin. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"23774","DOI":"10.3390\/ijms141223774","article-title":"The Dual Role of Smad7 in the Control of Cancer Growth and Metastasis","volume":"14","author":"Stolfi","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.immuni.2025.12.008","article-title":"Innate Lymphoid Cells Activated by the Cytokine TL1A Link Colitis to Emergency Granulopoiesis and the Recruitment of Tumor-Promoting Neutrophils","volume":"59","author":"Pires","year":"2026","journal-title":"Immunity"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/s41590-025-02149-z","article-title":"The IL-22\u2013Oncostatin M Axis Promotes Intestinal Inflammation and Tumorigenesis","volume":"26","author":"Cineus","year":"2025","journal-title":"Nat. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1186\/s12967-025-06565-5","article-title":"Unveiling the Hidden Dance: SPP1 + Macrophages Identified in Ulcerative Colitis Reveal Crosstalk with CHI3L1 + Fibroblasts","volume":"23","author":"Zhou","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Monteleone, G., Maresca, C., Colella, M., Pacifico, T., Congiu, D., Troncone, E., and Marafini, I. (2022). Targeting IL-34\/MCSF-1R Axis in Colon Cancer. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.917955"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Chalkidi, N., Melissari, M.-T., Henriques, A., Stavropoulou, A., Kollias, G., and Koliaraki, V. (2023). Activation and Functions of Col6a1+ Fibroblasts in Colitis-Associated Cancer. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25010148"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/s41420-021-00636-4","article-title":"Interleukin-34 Promotes Tumorigenic Signals for Colon Cancer Cells","volume":"7","author":"Marafini","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1053\/j.gastro.2010.01.058","article-title":"Inflammation and Colon Cancer","volume":"138","author":"Grivennikov","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Hisamatsu, T., Miyoshi, J., Oguri, N., Morikubo, H., Saito, D., Hayashi, A., Omori, T., and Matsuura, M. (2025). Inflammation-Associated Carcinogenesis in Inflammatory Bowel Disease: Clinical Features and Molecular Mechanisms. Cells, 14.","DOI":"10.3390\/cells14080567"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.cell.2010.01.025","article-title":"Immunity, Inflammation, and Cancer","volume":"140","author":"Grivennikov","year":"2010","journal-title":"Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nri3073","article-title":"Protective and Pathogenic Functions of Macrophage Subsets","volume":"11","author":"Murray","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1038\/s41590-019-0415-0","article-title":"Targeting Immune Cell Circuits and Trafficking in Inflammatory Bowel Disease","volume":"20","author":"Neurath","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1093\/ibd\/izab306","article-title":"TIPE2 Promotes Tumor Initiation But Inhibits Tumor Progression in Murine Colitis-Associated Colon Cancer","volume":"28","author":"Etwebi","year":"2022","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1038\/s41417-025-00917-5","article-title":"Integrated Multidimensional Bioinformatics Analysis of the Molecular Mechanisms of Ulcerative Colitis-Associated Colorectal Cancer and MMP1 as a Potential Therapeutic Target","volume":"32","author":"Yu","year":"2025","journal-title":"Cancer Gene Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s00384-024-04748-y","article-title":"Inflammatory Bowel Disease, Colitis, and Cancer: Unmasking the Chronic Inflammation Link","volume":"39","author":"Shahgoli","year":"2024","journal-title":"Int. J. Color. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s43556-025-00395-z","article-title":"Inflammatory Bowel Diseases: Pathological Mechanisms and Therapeutic Perspectives","volume":"7","author":"Yang","year":"2026","journal-title":"Mol. Biomed."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1056\/NEJMra1102942","article-title":"Ulcerative Colitis","volume":"365","author":"Danese","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1146\/annurev-immunol-030409-101225","article-title":"Inflammatory Bowel Disease","volume":"28","author":"Kaser","year":"2010","journal-title":"Annu. Rev. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1101\/gad.314617.118","article-title":"Roles of the Immune System in Cancer: From Tumor Initiation to Metastatic Progression","volume":"32","author":"Gonzalez","year":"2018","journal-title":"Genes Dev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/s41392-025-02264-1","article-title":"Pattern Recognition Receptors: Function, Regulation and Therapeutic Potential","volume":"10","author":"Chen","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1093\/ibd\/izad081","article-title":"Molecular Pathogenesis of Colitis-Associated Colorectal Cancer: Immunity, Genetics, and Intestinal Microecology","volume":"29","author":"Yin","year":"2023","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Sakai, K., De Velasco, M.A., Kura, Y., and Nishio, K. (2021). Transcriptome Profiling and Metagenomic Analysis Help to Elucidate Interactions in an Inflammation-Associated Cancer Mouse Model. Cancers, 13.","DOI":"10.3390\/cancers13153683"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Lyu, W., Zhang, Z., Liu, L., Sun, Y., Wang, B., Zhou, C., Liu, Z., and Feng, B. (2026). Gut Microbiota and Macrophage Crosstalk: Implications for Colitis-Associated Colorectal Cancer. Front. Cell. Infect. Microbiol., 16.","DOI":"10.3389\/fcimb.2026.1778244"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1136\/gutjnl-2020-320777","article-title":"Cross-Talk between the Gut Microbiota and Monocyte-like Macrophages Mediates an Inflammatory Response to Promote Colitis-Associated Tumourigenesis","volume":"70","author":"Yang","year":"2021","journal-title":"Gut"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Jasemi, S., Molicotti, P., Fais, M., Cossu, I., Simula, E.R., and Sechi, L.A. (2025). Biological Mechanisms of Enterotoxigenic Bacteroides Fragilis Toxin: Linking Inflammation, Colorectal Cancer, and Clinical Implications. Toxins, 17.","DOI":"10.3390\/toxins17060305"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Lee, C.-G., Hwang, S., Gwon, S.-Y., Park, C., Jo, M., Hong, J.-E., and Rhee, K.-J. (2022). Bacteroides Fragilis Toxin Induces Intestinal Epithelial Cell Secretion of Interleukin-8 by the E-Cadherin\/\u03b2-Catenin\/NF-\u03baB Dependent Pathway. Biomedicines, 10.","DOI":"10.3390\/biomedicines10040827"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1126\/science.1224820","article-title":"Intestinal Inflammation Targets Cancer-Inducing Activity of the Microbiota","volume":"338","author":"Arthur","year":"2012","journal-title":"Science"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1038\/s41467-021-21162-y","article-title":"Genomic Aberrations after Short-Term Exposure to Colibactin-Producing E. coli Transform Primary Colon Epithelial Cells","volume":"12","author":"Iftekhar","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.chom.2013.07.007","article-title":"Fusobacterium nucleatum Potentiates Intestinal Tumorigenesis and Modulates the Tumor-Immune Microenvironment","volume":"14","author":"Kostic","year":"2013","journal-title":"Cell Host Microbe"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Liu, L., Liang, L., Liang, H., Wang, M., Lu, B., Xue, M., Deng, J., and Chen, Y. (2019). Fusobacterium nucleatum Aggravates the Progression of Colitis by Regulating M1 Macrophage Polarization via AKT2 Pathway. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01324"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern Recognition Receptors and Inflammation","volume":"140","author":"Takeuchi","year":"2010","journal-title":"Cell"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Liu, N., Ling, R., Tang, X., Yu, Y., Zhou, Y., and Chen, D. (2022). Post-Translational Modifications of BRD4: Therapeutic Targets for Tumor. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.847701"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s12979-023-00383-3","article-title":"Toll-like Receptor 4 (TLR4): New Insight Immune and Aging","volume":"20","author":"Kim","year":"2023","journal-title":"Immun. Ageing"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"112413","DOI":"10.1016\/j.isci.2025.112413","article-title":"The PYRIN Domain Is Required for TLR4-Mediated Inflammation by PYHIN Family Members","volume":"28","author":"Iannucci","year":"2025","journal-title":"iScience"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1053\/j.gastro.2007.09.008","article-title":"Toll-Like Receptor-4 Promotes the Development of Colitis-Associated Colorectal Tumors","volume":"133","author":"Fukata","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1053\/j.gastro.2006.06.017","article-title":"Cox-2 Is Regulated by Toll-Like Receptor-4 (TLR4) Signaling: Role in Proliferation and Apoptosis in the Intestine","volume":"131","author":"Fukata","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1002\/ibd.20880","article-title":"Innate Immune Signaling by Toll-like Receptor-4 (TLR4) Shapes the Inflammatory Microenvironment in Colitis-Associated Tumors","volume":"15","author":"Fukata","year":"2009","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Pastille, E., Fa\u00dfnacht, T., Adamczyk, A., Ngo Thi Phuong, N., Buer, J., and Westendorf, A.M. (2021). Inhibition of TLR4 Signaling Impedes Tumor Growth in Colitis-Associated Colon Cancer. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.669747"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1002\/1878-0261.13475","article-title":"Pellino 3 Promotes the Colitis-associated Colorectal Cancer through Suppression of IRF4-mediated Negative Regulation of TLR4 Signalling","volume":"17","author":"Kim","year":"2023","journal-title":"Mol. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e21615","DOI":"10.1016\/j.heliyon.2023.e21615","article-title":"The Potential Role of miRNA in Regulating Macrophage Polarization","volume":"9","author":"Khayati","year":"2023","journal-title":"Heliyon"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s12964-021-00771-6","article-title":"TLR4 Signaling in the Development of Colitis-Associated Cancer and Its Possible Interplay with microRNA-155","volume":"19","author":"Guo","year":"2021","journal-title":"Cell Commun. Signal"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Bayraktar, R., Bertilaccio, M.T.S., and Calin, G.A. (2019). The Interaction Between Two Worlds: MicroRNAs and Toll-Like Receptors. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01053"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen Recognition and Innate Immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1084\/jem.20100199","article-title":"MyD88-Mediated Signaling Prevents Development of Adenocarcinomas of the Colon: Role of Interleukin 18","volume":"207","author":"Salcedo","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s00535-004-1492-9","article-title":"MyD88-Deficient Mice Develop Severe Intestinal Inflammation in Dextran Sodium Sulfate Colitis","volume":"40","author":"Araki","year":"2005","journal-title":"J. Gastroenterol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1007\/s10637-022-01218-6","article-title":"Blockade of Myd88 Signaling by a Novel MyD88 Inhibitor Prevents Colitis-Associated Colorectal Cancer Development by Impairing Myeloid-Derived Suppressor Cells","volume":"40","author":"Wang","year":"2022","journal-title":"Investig. New Drugs"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Javaid, N., and Choi, S. (2020). Toll-like Receptors from the Perspective of Cancer Treatment. Cancers, 12.","DOI":"10.3390\/cancers12020297"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1002\/ibd.20142","article-title":"Activation of Toll-like Receptor 3 Protects against DSS-Induced Acute Colitis","volume":"13","author":"Wu","year":"2007","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"30308","DOI":"10.1038\/s41598-024-76954-1","article-title":"Toll-like Receptor 3 Signaling Attenuated Colitis-Associated Cancer Development in Mice","volume":"14","author":"Chung","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1126\/science.1220363","article-title":"TLR13 Recognizes Bacterial 23S rRNA Devoid of Erythromycin Resistance\u2013Forming Modification","volume":"337","author":"Oldenburg","year":"2012","journal-title":"Science"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1002\/ijc.35089","article-title":"Toll-like Receptor 13-mediated Signaling Protects against the Development of Colon Cancer","volume":"155","author":"Rafique","year":"2024","journal-title":"Int. J. Cancer"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"6425","DOI":"10.1002\/jcp.26429","article-title":"Macrophage Plasticity, Polarization, and Function in Health and Disease","volume":"233","author":"Mohammadian","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/nri2448","article-title":"Exploring the Full Spectrum of Macrophage Activation","volume":"8","author":"Mosser","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.it.2004.09.015","article-title":"The Chemokine System in Diverse Forms of Macrophage Activation and Polarization","volume":"25","author":"Mantovani","year":"2004","journal-title":"Trends Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"168176","DOI":"10.1016\/j.bbadis.2026.168176","article-title":"Leveraging Macrophage Plasticity for Precision-Targeted Tumor Immunotherapy","volume":"1872","author":"Li","year":"2026","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Basis Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1186\/s12964-023-01386-9","article-title":"Macrophage Polarization in Inflammatory Bowel Disease","volume":"21","author":"Zhang","year":"2023","journal-title":"Cell Commun. Signal."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"6743","DOI":"10.7150\/thno.43938","article-title":"An Ultralow Dose of the NADPH Oxidase Inhibitor Diphenyleneiodonium (DPI) Is an Economical and Effective Therapeutic Agent for the Treatment of Colitis-Associated Colorectal Cancer","volume":"10","author":"Kuai","year":"2020","journal-title":"Theranostics"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Eom, Y.W., Akter, R., Li, W., Lee, S., Hwang, S., Kim, J., and Cho, M.-Y. (2020). M1 Macrophages Promote TRAIL Expression in Adipose Tissue-Derived Stem Cells, Which Suppresses Colitis-Associated Colon Cancer by Increasing Apoptosis of CD133+ Cancer Stem Cells and Decreasing M2 Macrophage Population. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113887"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Brancewicz, J., W\u00f3jcik, N., Sarnowska, Z., Robak, J., and Kr\u00f3l, M. (2025). The Multifaceted Role of Macrophages in Biology and Diseases. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26052107"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Yao, Y., Xu, X.-H., and Jin, L. (2019). Macrophage Polarization in Physiological and Pathological Pregnancy. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00792"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/JLB.3RU1018-378RR","article-title":"M2b Macrophage Polarization and Its Roles in Diseases","volume":"106","author":"Wang","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Ambarus, C.A., Santegoets, K.C.M., Van Bon, L., Wenink, M.H., Tak, P.P., Radstake, T.R.D.J., and Baeten, D.L.P. (2012). Soluble Immune Complexes Shift the TLR-Induced Cytokine Production of Distinct Polarized Human Macrophage Subsets towards IL-10. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035994"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.immuni.2016.02.015","article-title":"Macrophages in Tissue Repair, Regeneration, and Fibrosis","volume":"44","author":"Wynn","year":"2016","journal-title":"Immunity"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Luo, M., Zhao, F., Cheng, H., Su, M., and Wang, Y. (2024). Macrophage Polarization: An Important Role in Inflammatory Diseases. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1352946"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1002\/jso.23110","article-title":"Tumor-associated Macrophages Promote Angiogenesis and Lymphangiogenesis of Gastric Cancer","volume":"106","author":"Wu","year":"2012","journal-title":"J. Surg. Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1007\/s10753-013-9621-3","article-title":"The Adenosine-Dependent Angiogenic Switch of Macrophages to an M2-Like Phenotype Is Independent of Interleukin-4 Receptor Alpha (IL-4R\u03b1) Signaling","volume":"36","author":"Ferrante","year":"2013","journal-title":"Inflammation"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2303177","DOI":"10.1002\/advs.202303177","article-title":"NAMPT-Driven M2 Polarization of Tumor-Associated Macrophages Leads to an Immunosuppressive Microenvironment in Colorectal Cancer","volume":"11","author":"Hong","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"115576","DOI":"10.1016\/j.intimp.2025.115576","article-title":"Complement Component C6 Deficiency Exacerbates Colorectal Tumorigenesis by Abolishing Membrane Attack Complex Formation and Potentiating M2-like Tumor-Associated Macrophage Responses","volume":"166","author":"Hao","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1038\/s41467-025-56440-6","article-title":"The Ubiquitin Ligase Pellino1 Targets STAT3 to Regulate Macrophage-Mediated Inflammation and Tumor Development","volume":"16","author":"Hwang","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"jjaf184","DOI":"10.1093\/ecco-jcc\/jjaf184","article-title":"Spatial Transcriptomics and Immunophenotyping Uncover Chronic Inflammation-Induced Immune Adaptations Favoring Dysplasia Development in Patients at Risk of Colitis-Associated Cancer","volume":"19","author":"Frigerio","year":"2025","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"4303","DOI":"10.1158\/0008-5472.CAN-18-0116","article-title":"Ornithine Decarboxylase in Macrophages Exacerbates Colitis and Promotes Colitis-Associated Colon Carcinogenesis by Impairing M1 Immune Responses","volume":"78","author":"Singh","year":"2018","journal-title":"Cancer Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s12943-024-02108-6","article-title":"Discovery of Vitexin as a Novel VDR Agonist That Mitigates the Transition from Chronic Intestinal Inflammation to Colorectal Cancer","volume":"23","author":"Chen","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Dell\u2019Anna, G., Fanizzi, F., Zilli, A., Furfaro, F., Solitano, V., Parigi, T.L., Ciliberto, A., Fanizza, J., Mandarino, F.V., and Fuccio, L. (2025). The Role of Vitamin D in Inflammatory Bowel Diseases: From Deficiency to Targeted Therapeutics and Precise Nutrition Strategies. Nutrients, 17.","DOI":"10.3390\/nu17132167"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"933","DOI":"10.3748\/wjg.v22.i3.933","article-title":"Protective Links between Vitamin D, Inflammatory Bowel Disease and Colon Cancer","volume":"22","author":"Meeker","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/s41419-022-04775-z","article-title":"Interaction between Macrophages and Ferroptosis","volume":"13","author":"Yang","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/s41423-025-01380-w","article-title":"Neutrophils as Critical Orchestrators of Chronic Inflammation","volume":"23","author":"Torfs","year":"2026","journal-title":"Cell Mol. Immunol."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Zhang, C., Zhang, J., Zhang, Y., Song, Z., Bian, J., Yi, H., and Ma, Z. (2023). Identifying Neutrophil-Associated Subtypes in Ulcerative Colitis and Confirming Neutrophils Promote Colitis-Associated Colorectal Cancer. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1095098"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"925","DOI":"10.2147\/JIR.S497701","article-title":"Neutrophils: From Inflammatory Bowel Disease to Colitis-Associated Colorectal Cancer","volume":"18","author":"Chen","year":"2025","journal-title":"J. Inflamm. Res."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Ortega-Zapero, M., Gomez-Bris, R., Pascual-Laguna, I., Saez, A., and Gonzalez-Granado, J.M. (2025). Neutrophils and NETs in Pathophysiology and Treatment of Inflammatory Bowel Disease. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26157098"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"82443378","DOI":"10.1155\/2021\/8243378","article-title":"Interplay between Extracellular Matrix and Neutrophils in Diseases","volume":"2021","author":"Zhu","year":"2021","journal-title":"J. Immunol. Res."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Yu, S., Zhang, M., Niu, W., Huang, Y., Dou, Z., Tian, B., Yang, L., and Lu, J. (2026). Neutrophils in Inflammatory Bowel Disease: Disease-Promoting versus Protective Functions. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1750743"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/s41385-020-0297-3","article-title":"Intestinal Epithelium-Derived BATF3 Promotes Colitis-Associated Colon Cancer through Facilitating CXCL5-Mediated Neutrophils Recruitment","volume":"14","author":"Lin","year":"2021","journal-title":"Mucosal Immunol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"101891","DOI":"10.1016\/j.redox.2021.101891","article-title":"Immune Cell\u2014Produced ROS and Their Impact on Tumor Growth and Metastasis","volume":"42","author":"Kennel","year":"2021","journal-title":"Redox Biol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1080\/15548627.2025.2489335","article-title":"Neutrophil-Derived Serine Proteases Induce FOXA2-Mediated Autophagy Dysfunction and Exacerbate Colitis-Associated Carcinogenesis via Protease Activated Receptor 2","volume":"21","author":"Yuan","year":"2025","journal-title":"Autophagy"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"eabd1453","DOI":"10.1126\/sciadv.abd1453","article-title":"Agonist Anti-ChemR23 mAb Reduces Tissue Neutrophil Accumulation and Triggers Chronic Inflammation Resolution","volume":"7","author":"Trilleaud","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nm.2278","article-title":"Histamine Deficiency Promotes Inflammation-Associated Carcinogenesis through Reduced Myeloid Maturation and Accumulation of CD11b+Ly6G+ Immature Myeloid Cells","volume":"17","author":"Yang","year":"2011","journal-title":"Nat. Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.jcmgh.2021.11.003","article-title":"Loss of H2R Signaling Disrupts Neutrophil Homeostasis and Promotes Inflammation-Associated Colonic Tumorigenesis in Mice","volume":"13","author":"Shi","year":"2022","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/ecco-jcc\/jjy215","article-title":"Neutrophil Extracellular Traps Sustain Inflammatory Signals in Ulcerative Colitis","volume":"13","author":"Dinallo","year":"2019","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"eadj1397","DOI":"10.1126\/sciadv.adj1397","article-title":"NET Formation Is a Default Epigenetic Program Controlled by PAD4 in Apoptotic Neutrophils","volume":"9","author":"Zhu","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1007\/s12016-020-08804-7","article-title":"A Review of Neutrophil Extracellular Traps (NETs) in Disease: Potential Anti-NETs Therapeutics","volume":"61","author":"Mutua","year":"2021","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1136\/gutjnl-2021-324725","article-title":"Neutrophils Prevent Rectal Bleeding in Ulcerative Colitis by Peptidyl-Arginine Deiminase-4-Dependent Immunothrombosis","volume":"71","author":"Leppkes","year":"2022","journal-title":"Gut"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"4179","DOI":"10.1007\/s00018-014-1683-3","article-title":"Neutrophil Extracellular Traps in Cancer Progression","volume":"71","author":"Spicer","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"107589","DOI":"10.4251\/wjgo.v17.i7.107589","article-title":"Exploring the Role of Neutrophil Extracellular Traps in Colorectal Cancer: Insights from Single-Cell Sequencing","volume":"17","author":"Xu","year":"2025","journal-title":"World J. Gastrointest. Oncol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.7150\/ijbs.122290","article-title":"Neutrophil Extracellular Traps Prime the ZBP1-cGAS Sensor Complex, Triggering Necroptosis and Inflammatory Injury in Acute Pancreatitis","volume":"22","author":"Zhang","year":"2026","journal-title":"Int. J. Biol. Sci."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1186\/s13046-023-02817-8","article-title":"Fusobacterium nucleatum-Triggered Neutrophil Extracellular Traps Facilitate Colorectal Carcinoma Progression","volume":"42","author":"Kong","year":"2023","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Manilla, V., Di Tommaso, N., Santopaolo, F., Gasbarrini, A., and Ponziani, F.R. (2023). Endotoxemia and Gastrointestinal Cancers: Insight into the Mechanisms Underlying a Dangerous Relationship. Microorganisms, 11.","DOI":"10.3390\/microorganisms11020267"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1158\/0008-5472.CAN-20-3222","article-title":"Platelet TLR4-ERK5 Axis Facilitates NET-Mediated Capturing of Circulating Tumor Cells and Distant Metastasis after Surgical Stress","volume":"81","author":"Ren","year":"2021","journal-title":"Cancer Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1080\/13880209.2021.2017981","article-title":"Effect of Huangqin Decoction on Regulating Intestinal Flora in Colitis Mice Characterized as Inhibition of the NOD2-Dependent Pathway","volume":"60","author":"Huang","year":"2022","journal-title":"Pharm. Biol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"154454","DOI":"10.1016\/j.phymed.2022.154454","article-title":"Huang Qin Decoction Inhibits the Initiation of Experimental Colitis Associated Carcinogenesis by Controlling the PAD4 Dependent NETs","volume":"107","author":"Pan","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"119337","DOI":"10.1016\/j.jep.2025.119337","article-title":"Glycyrrhizic Acid Reduces Neutrophil Extracellular Trap Formation to Ameliorate Colitis-Associated Colorectal Cancer by Inhibiting Peptidylarginine Deiminase 4","volume":"341","author":"Chen","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Demkow, U. (2021). Neutrophil Extracellular Traps (NETs) in Cancer Invasion, Evasion and Metastasis. Cancers, 13.","DOI":"10.3390\/cancers13174495"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"5846","DOI":"10.7150\/thno.111096","article-title":"Targeting Neutrophil Extracellular Traps in Cancer Progression and Metastasis","volume":"15","author":"Zhang","year":"2025","journal-title":"Theranostics"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1189\/jlb.0113050","article-title":"The Role and Potential Therapeutic Application of Myeloid-Derived Suppressor Cells in TNBS-Induced Colitis","volume":"94","author":"Guan","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"5039","DOI":"10.1158\/1078-0432.CCR-13-0278","article-title":"Downregulation of Hematopoietic MUC1 during Experimental Colitis Increases Tumor-Promoting Myeloid-Derived Suppressor Cells","volume":"19","author":"Poh","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Delgado-Ramirez, Y., Baltazar-Perez, I., Martinez, Y., Callejas, B.E., Medina-Andrade, I., Olgu\u00edn, J.E., Delgado-Buenrostro, N.L., Chirino, Y.I., Terrazas, L.I., and Leon-Cabrera, S. (2021). STAT1 Is Required for Decreasing Accumulation of Granulocytic Cells via IL-17 during Initial Steps of Colitis-Associated Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147695"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Shang, K., Bai, Y.-P., Wang, C., Wang, Z., Gu, H.-Y., Du, X., Zhou, X.-Y., Zheng, C.-L., Chi, Y.-Y., and Mukaida, N. (2012). Crucial Involvement of Tumor-Associated Neutrophils in the Regulation of Chronic Colitis-Associated Carcinogenesis in Mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051848"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"3127","DOI":"10.1172\/JCI61067","article-title":"Inhibition of CXCR2 Profoundly Suppresses Inflammation-Driven and Spontaneous Tumorigenesis","volume":"122","author":"Jamieson","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"3659","DOI":"10.7150\/thno.32126","article-title":"RIP3 Promotes Colitis-Associated Colorectal Cancer by Controlling Tumor Cell Proliferation and CXCL1-Induced Immune Suppression","volume":"9","author":"Liu","year":"2019","journal-title":"Theranostics"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1038\/s41423-025-01326-2","article-title":"The Gut Microbiota in Cancer Immunity and Immunotherapy","volume":"22","author":"Xie","year":"2025","journal-title":"Cell Mol. Immunol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s00281-014-0418-8","article-title":"The Multiple Faces of Leukocyte Interstitial Migration","volume":"36","author":"Germain","year":"2014","journal-title":"Semin. Immunopathol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1038\/mi.2014.123","article-title":"IL-1\u03b2 in Eosinophil-Mediated Small Intestinal Homeostasis and IgA Production","volume":"8","author":"Jung","year":"2015","journal-title":"Mucosal Immunol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.3748\/wjg.v25.i27.3503","article-title":"Eosinophils in the Gastrointestinal Tract and Their Role in the Pathogenesis of Major Colorectal Disorders","volume":"25","author":"Loktionov","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1038\/ajg.2016.418","article-title":"Histological Disease Activity as a Predictor of Clinical Relapse Among Patients with Ulcerative Colitis: Systematic Review and Meta-Analysis","volume":"111","author":"Park","year":"2016","journal-title":"Am. J. Gastroenterol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1158\/1055-9965.EPI-11-0360","article-title":"Inverse Association of Eosinophil Count with Colorectal Cancer Incidence: Atherosclerosis Risk in Communities Study","volume":"20","author":"Prizment","year":"2011","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1016\/j.jaci.2008.04.005","article-title":"A Novel IL-1 Family Cytokine, IL-33, Potently Activates Human Eosinophils","volume":"121","author":"Cherry","year":"2008","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"4469","DOI":"10.1172\/JCI88625","article-title":"IL-33 Regulates the IgA-Microbiota Axis to Restrain IL-1\u03b1\u2013Dependent Colitis and Tumorigenesis","volume":"126","author":"Malik","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1776059","DOI":"10.1080\/2162402X.2020.1776059","article-title":"IL-33 Reduces Tumor Growth in Models of Colorectal Cancer with the Help of Eosinophils","volume":"9","author":"Kienzl","year":"2020","journal-title":"OncoImmunology"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"6540","DOI":"10.1038\/s41388-021-02046-3","article-title":"CCL11 Exacerbates Colitis and Inflammation-Associated Colon Tumorigenesis","volume":"40","author":"Polosukhina","year":"2021","journal-title":"Oncogene"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"e1002721","DOI":"10.1080\/2162402X.2014.1002721","article-title":"IL-15 Suppresses Colitis-Associated Colon Carcinogenesis by Inducing Antitumor Immunity","volume":"4","author":"Bahri","year":"2015","journal-title":"OncoImmunology"},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Abel, A.M., Yang, C., Thakar, M.S., and Malarkannan, S. (2018). Natural Killer Cells: Development, Maturation, and Clinical Utilization. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01869"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.bj.2016.01.003","article-title":"Antigen Specificity of Invariant Natural Killer T-Cells","volume":"38","author":"Birkholz","year":"2015","journal-title":"Biomed. J."},{"key":"ref_164","first-page":"71","article-title":"Natural Killer T Cells (NKT Cells) Functions in Malignancies","volume":"3","author":"Nourozian","year":"2018","journal-title":"Asian Pac. J. Cancer Biol."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Lee, S.W., Park, H.J., Van Kaer, L., and Hong, S. (2024). Role of CD1d and iNKT Cells in Regulating Intestinal Inflammation. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1343718"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1093\/ecco-jcc\/jjac049","article-title":"IL10 Secretion Endows Intestinal Human iNKT Cells with Regulatory Functions Towards Pathogenic T Lymphocytes","volume":"16","author":"Burrello","year":"2022","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1136\/gutjnl-2013-305671","article-title":"IL-13R\u03b12-Bearing, Type II NKT Cells Reactive to Sulfatide Self-Antigen Populate the Mucosa of Ulcerative Colitis","volume":"63","author":"Fuss","year":"2014","journal-title":"Gut"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1172\/JCI19836","article-title":"Nonclassical CD1d-Restricted NK T Cells That Produce IL-13 Characterize an Atypical Th2 Response in Ulcerative Colitis","volume":"113","author":"Fuss","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.1365-3083.2011.02607.x","article-title":"Role of Natural Killer T Cells in the Mouse Colitis-Associated Colon Cancer Model","volume":"75","author":"Yoshioka","year":"2012","journal-title":"Scand. J. Immunol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"aaa6566","DOI":"10.1126\/science.aaa6566","article-title":"Innate Lymphoid Cells: A New Paradigm in Immunology","volume":"348","author":"Eberl","year":"2015","journal-title":"Science"},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Panda, S.K., and Colonna, M. (2019). Innate Lymphoid Cells in Mucosal Immunity. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00861"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/s41422-020-0323-8","article-title":"Innate Lymphoid Cells Control Signaling Circuits to Regulate Tissue-Specific Immunity","volume":"30","author":"Klose","year":"2020","journal-title":"Cell Res."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Huang, Q., Cao, W., Mielke, L.A., Seillet, C., Belz, G.T., and Jacquelot, N. (2020). Innate Lymphoid Cells in Colorectal Cancers: A Double-Edged Sword. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.03080"},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Loyon, R., Jary, M., Salom\u00e9, B., Gomez-Cadena, A., Galaine, J., Kroemer, M., Romero, P., Trabanelli, S., Adot\u00e9vi, O., and Borg, C. (2019). Peripheral Innate Lymphoid Cells Are Increased in First Line Metastatic Colorectal Carcinoma Patients: A Negative Correlation with Th1 Immune Responses. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02121"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"100353","DOI":"10.1016\/j.xcrm.2021.100353","article-title":"Single-Cell Transcriptomic Landscape Reveals Tumor Specific Innate Lymphoid Cells Associated with Colorectal Cancer Progression","volume":"2","author":"Qi","year":"2021","journal-title":"Cell Rep. Med."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Huang, Q., Jacquelot, N., Preaudet, A., Hediyeh-zadeh, S., Souza-Fonseca-Guimaraes, F., McKenzie, A.N.J., Hansbro, P.M., Davis, M.J., Mielke, L.A., and Putoczki, T.L. (2021). Type 2 Innate Lymphoid Cells Protect against Colorectal Cancer Progression and Predict Improved Patient Survival. Cancers, 13.","DOI":"10.3390\/cancers13030559"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"5015","DOI":"10.1016\/j.cell.2021.07.029","article-title":"Dysregulation of ILC3s Unleashes Progression and Immunotherapy Resistance in Colon Cancer","volume":"184","author":"Goc","year":"2021","journal-title":"Cell"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1002\/jgh3.12398","article-title":"TL1A (TNFSF15) Genotype Affects the Long-term Therapeutic Outcomes of anti-TNFa Antibodies for Crohn\u2019s Disease Patients","volume":"4","author":"Endo","year":"2020","journal-title":"JGH Open"},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Tettoni, E., Gabbiadini, R., Dal Buono, A., Privitera, G., Vadal\u00e0, V., Migliorisi, G., Bertoli, P., Quadarella, A., Bezzio, C., and Armuzzi, A. (2025). TL1A as a Target in Inflammatory Bowel Disease: Exploring Mechanisms and Therapeutic Potential. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26115017"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1007\/s10620-018-5126-0","article-title":"Tumor Necrosis Factor Ligand-Related Molecule 1A Regulates the Occurrence of Colitis-Associated Colorectal Cancer","volume":"63","author":"Niu","year":"2018","journal-title":"Dig. Dis. Sci."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/ng.3742","article-title":"Dynamics of Clonal Evolution in Myelodysplastic Syndromes","volume":"49","author":"Makishima","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1038\/s41590-024-01921-x","article-title":"Nucleophosmin 1 Promotes Mucosal Immunity by Supporting Mitochondrial Oxidative Phosphorylation and ILC3 Activity","volume":"25","author":"Zhao","year":"2024","journal-title":"Nat. Immunol."},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Kelemen, K. (2022). The Role of Nucleophosmin 1 (NPM1) Mutation in the Diagnosis and Management of Myeloid Neoplasms. Life, 12.","DOI":"10.3390\/life12010109"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"e56034","DOI":"10.15252\/embr.202256034","article-title":"BTNL2 Promotes Colitis-associated Tumorigenesis in Mice by Regulating IL-22 Production","volume":"24","author":"Peng","year":"2023","journal-title":"EMBO Rep."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.immuni.2021.03.018","article-title":"Interleukin-17D Regulates Group 3 Innate Lymphoid Cell Function through Its Receptor CD93","volume":"54","author":"Huang","year":"2021","journal-title":"Immunity"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00281-009-0161-8","article-title":"Colitis-Associated Cancer: The Role of T Cells in Tumor Development","volume":"31","author":"Waldner","year":"2009","journal-title":"Semin. Immunopathol."},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Toor, S.M., Murshed, K., Al-Dhaheri, M., Khawar, M., Abu Nada, M., and Elkord, E. (2019). Immune Checkpoints in Circulating and Tumor-Infiltrating CD4+ T Cell Subsets in Colorectal Cancer Patients. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02936"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1002\/ijc.21639","article-title":"Predominant T Helper Type 2-inflammatory Responses Promote Murine Colon Cancers","volume":"118","author":"Osawa","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/s41423-026-01391-1","article-title":"Lytic IFN\u03b3 Is Stored in Cytotoxic Granules and Coreleased with Granzyme B to Mediate Cytotoxic T Lymphocyte Killing","volume":"23","author":"Li","year":"2026","journal-title":"Cell Mol. Immunol."},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"Troncone, E., Marafini, I., Stolfi, C., and Monteleone, G. (2021). Involvement of Smad7 in Inflammatory Diseases of the Gut and Colon Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22083922"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"7423","DOI":"10.1158\/0008-5472.CAN-11-1895","article-title":"Smad7 Expression in T Cells Prevents Colitis-Associated Cancer","volume":"71","author":"Rizzo","year":"2011","journal-title":"Cancer Res."},{"key":"ref_192","doi-asserted-by":"crossref","unstructured":"Zhang, H., Shi, Y., Lin, C., He, C., Wang, S., Li, Q., Sun, Y., and Li, M. (2024). Overcoming Cancer Risk in Inflammatory Bowel Disease: New Insights into Preventive Strategies and Pathogenesis Mechanisms Including Interactions of Immune Cells, Cancer Signaling Pathways, and Gut Microbiota. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1338918"},{"key":"ref_193","first-page":"3092","article-title":"Intestinal Inflammation and Colorectal Cancer: A Double-Edged Sword?","volume":"17","author":"Rizzo","year":"2011","journal-title":"World J. Gastroenterol."},{"key":"ref_194","doi-asserted-by":"crossref","unstructured":"Schmitt, H., Neurath, M.F., and Atreya, R. (2021). Role of the IL23\/IL17 Pathway in Crohn\u2019s Disease. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.622934"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1136\/gut.43.6.735","article-title":"Interleukin 12 and Th1 Responses in Inflammatory Bowel Disease","volume":"43","author":"Pallone","year":"1998","journal-title":"Gut"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/S0016-5085(99)70392-6","article-title":"Anti\u2013Interleukin 12 Treatment Regulates Apoptosis of Th1 T Cells in Experimental Colitis in Mice","volume":"117","author":"Fuss","year":"1999","journal-title":"Gastroenterology"},{"key":"ref_197","unstructured":"Bossuyt, P., Rahier, J.-F., Baert, F., Louis, E., Macken, E., Lobaton, T., Busschaert, J., Peeters, H., Dewint, P., and Franchimont, D. (Gastroenterology, 2026). The Effect of Dose-Intensification after Secondary Loss of Response to Ustekinumab in Crohn\u2019s Disease: Results of the REScUE Study, Gastroenterology, in press."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1093\/ecco-jcc\/jjz209","article-title":"Belgian IBD Research Group [BIRD] Position Statement 2019 on the Use of Adalimumab Biosimilars in Inflammatory Bowel Diseases","volume":"14","author":"Somers","year":"2020","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1080\/14712598.2025.2539423","article-title":"Advanced Therapies Targeting IL-23: Clinical Outcomes in Ulcerative Colitis","volume":"25","author":"Salvatori","year":"2025","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1001\/jama.2024.12414","article-title":"Risankizumab for Ulcerative Colitis: Two Randomized Clinical Trials","volume":"332","author":"Louis","year":"2024","journal-title":"JAMA"},{"key":"ref_201","doi-asserted-by":"crossref","unstructured":"Sands, B.E., Barnes, E.L., D\u2019Haens, G., Hisamatsu, T., Regueiro, M., Kelly, C.R., Laharie, D., Hozak, R.R., Yu, G., and Gandhi R, A. (Clin. Gastroenterol. Hepatol., 2026). Mirikizumab Long-Term Efficacy and Safety in Patients with Crohn\u2019s Disease: Results from the VIVID-2 Open-Label Extension Trial, Clin. Gastroenterol. Hepatol., in press.","DOI":"10.1016\/j.cgh.2026.01.049"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"2350460","DOI":"10.1002\/eji.202350460","article-title":"TGF-\u03b21 Signaling and Smad7 Control T-cell Responses in Health and Immune-mediated Disorders","volume":"53","author":"Laudisi","year":"2023","journal-title":"Eur. J. Immunol."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"114961","DOI":"10.1016\/j.isci.2026.114961","article-title":"Role and Progression of Bile Acid Metabolism in Mediating Th17\/Treg Homeostasis in Inflammatory Bowel Disease","volume":"29","author":"Yue","year":"2026","journal-title":"iScience"},{"key":"ref_204","doi-asserted-by":"crossref","unstructured":"Hu, Y., Yang, Y., Li, Y., Zhang, Q., Zhang, W., Jia, J., Han, Z., and Wang, J. (2025). Th17\/Treg Imbalance in Inflammatory Bowel Disease: Immunological Mechanisms and Microbiota-Driven Regulation. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1651063"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"526","DOI":"10.3109\/08830185.2013.823421","article-title":"Th17 Cytokines in Inflammatory Bowel Diseases: Discerning the Good from the Bad","volume":"32","author":"Troncone","year":"2013","journal-title":"Int. Rev. Immunol."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1093\/ecco-jcc\/jjad119","article-title":"An Intestinal Th17 Subset Is Associated with Inflammation in Crohn\u2019s Disease and Activated by Adherent-Invasive Escherichia coli","volume":"17","author":"Paroni","year":"2023","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"jjae134","DOI":"10.1093\/ecco-jcc\/jjae134","article-title":"Deficiency in Epithelium RAD50 Aggravates UC via IL-6-Mediated JAK1\/2-STAT3 Signaling and Promotes Development of Colitis-Associated Cancer in Mice","volume":"19","author":"Zhang","year":"2025","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1084\/jem.20111106","article-title":"Involvement of Interleukin-21 in the Regulation of Colitis-Associated Colon Cancer","volume":"208","author":"Stolfi","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1136\/gut.2006.093187","article-title":"Control of Matrix Metalloproteinase Production in Human Intestinal Fibroblasts by Interleukin 21","volume":"55","author":"Monteleone","year":"2006","journal-title":"Gut"},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Lv, Y., Jin, Y.-L., Zhou, Z., Liao, J.-B., Zhang, Z.-Q., Tang, L.-Y., Xie, X.-H., Wang, S., Jin, M.-X., and Liu, H.-Y. (2026). The Interaction between Dendritic Cells and T Follicular Helper Cells Drives Inflammatory Bowel Disease: A Review. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1725349"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1136\/gutjnl-2011-300612","article-title":"Interleukin 21 Controls Tumour Growth and Tumour Immunosurveillance in Colitis-Associated Tumorigenesis in Mice","volume":"60","author":"Jauch","year":"2011","journal-title":"Gut"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1136\/gut.2007.130922","article-title":"Blockade of Transforming Growth Factor \u03b2 Upregulates T-Box Transcription Factor T-Bet, and Increases T Helper Cell Type 1 Cytokine and Matrix Metalloproteinase-3 Production in the Human Gut Mucosa","volume":"57","author":"Pickard","year":"2008","journal-title":"Gut"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.tcb.2020.06.003","article-title":"The Roles of CD8+ T Cell Subsets in Antitumor Immunity","volume":"30","author":"Ohashi","year":"2020","journal-title":"Trends Cell Biol."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1186\/s12967-024-05134-6","article-title":"CD8+ T Cell-Based Cancer Immunotherapy","volume":"22","author":"Chen","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_215","doi-asserted-by":"crossref","unstructured":"Bai, Z., Zhou, Y., Ye, Z., Xiong, J., Lan, H., and Wang, F. (2022). Tumor-Infiltrating Lymphocytes in Colorectal Cancer: The Fundamental Indication and Application on Immunotherapy. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.808964"},{"key":"ref_216","doi-asserted-by":"crossref","unstructured":"Schardey, J., Lu, C., Neumann, J., Wirth, U., Li, Q., Jiang, T., Zimmermann, P., Andrassy, J., Bazhin, A.V., and Werner, J. (2023). Differential Immune Infiltration Profiles in Colitis-Associated Colorectal Cancer versus Sporadic Colorectal Cancer. Cancers, 15.","DOI":"10.3390\/cancers15194743"},{"key":"ref_217","doi-asserted-by":"crossref","unstructured":"Barbosa, A.M., Martinho, O., Nogueira, R., Campos, J., Lobo, L., Pinto, H., Longatto-Filho, A., Castro, A.G., Martins, S.F., and Torrado, E. (2021). Increased CD3+, CD8+, or FoxP3+ T Lymphocyte Infiltrations Are Associated with the Pathogenesis of Colorectal Cancer but Not with the Overall Survival of Patients. Biology, 10.","DOI":"10.3390\/biology10080808"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1093\/ecco-jcc\/jjv211","article-title":"Enrichment of Circulating and Mucosal Cytotoxic CD8+ T Cells Is Associated with Postoperative Endoscopic Recurrence in Patients with Crohn\u2019s Disease","volume":"10","author":"Boschetti","year":"2016","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.immuni.2019.06.025","article-title":"Inflammation and Cancer: Triggers, Mechanisms, and Consequences","volume":"51","author":"Greten","year":"2019","journal-title":"Immunity"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1002\/ibd.21107","article-title":"Perforin Deficiency Attenuates Inflammation and Tumor Growth in Colitis-Associated Cancer","volume":"16","author":"Waldner","year":"2010","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jaci.2023.09.025","article-title":"Regulatory T Cells in Dominant Immunologic Tolerance","volume":"153","author":"Georgiev","year":"2024","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_222","doi-asserted-by":"crossref","unstructured":"Schmidt, A., Oberle, N., and Krammer, P.H. (2012). Molecular Mechanisms of Treg-Mediated T Cell Suppression. Front. Immunol., 3.","DOI":"10.3389\/fimmu.2012.00051"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"15179","DOI":"10.1038\/srep15179","article-title":"Prognostic Value of Tumor-Infiltrating FoxP3+ Regulatory T Cells in Cancers: A Systematic Review and Meta-Analysis","volume":"5","author":"Shang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1200\/JCO.2008.18.7229","article-title":"Tumor-Infiltrating FOXP3+ T Regulatory Cells Show Strong Prognostic Significance in Colorectal Cancer","volume":"27","author":"Salama","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"6515","DOI":"10.4049\/jimmunol.1001671","article-title":"Runx3 Is Required for Full Activation of Regulatory T Cells To Prevent Colitis-Associated Tumor Formation","volume":"186","author":"Sugai","year":"2011","journal-title":"J. Immunol."},{"key":"ref_226","doi-asserted-by":"crossref","unstructured":"Yu, H., Yang, R., Li, M., Li, D., and Xu, Y. (2025). The Role of Treg Cells in Colorectal Cancer and the Immunotherapy Targeting Treg Cells. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1574327"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"111051","DOI":"10.1016\/j.celrep.2022.111051","article-title":"B Cell-Mediated Regulatory Mechanisms Control Tumor-Promoting Intestinal Inflammation","volume":"40","author":"Melcher","year":"2022","journal-title":"Cell Rep."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"6083","DOI":"10.4049\/jimmunol.1302238","article-title":"Plasma Cells in the Mucosa of Patients with Inflammatory Bowel Disease Produce Granzyme B and Possess Cytotoxic Activities","volume":"192","author":"Cupi","year":"2014","journal-title":"J. Immunol."},{"key":"ref_229","doi-asserted-by":"crossref","unstructured":"Pousette, J., Johansson, A., J\u00f6nsson, C., Fornander, T., Lindstr\u00f6m, L.S., Olsson, H., and Perez-Tenorio, G. (2022). Prognostic and Predictive Significance of Stromal Tumor-Infiltrating Lymphocytes (sTILs) in ER-Positive\/HER2\u2212Negative Postmenopausal Breast Cancer Patients. Cancers, 14.","DOI":"10.3390\/cancers14194844"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s00262-018-2250-9","article-title":"CD19+ Tumor-Infiltrating B-Cells Prime CD4+ T-Cell Immunity and Predict Platinum-Based Chemotherapy Efficacy in Muscle-Invasive Bladder Cancer","volume":"68","author":"Jiang","year":"2019","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1056\/NEJMc2508023","article-title":"CD19 CAR T-Cell Therapy in Multidrug-Resistant Ulcerative Colitis","volume":"393","author":"Atreya","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_232","doi-asserted-by":"crossref","unstructured":"Marafini, I., Salvatori, S., Troncone, E., and Monteleone, G. (Gastroenterology, 2025). CD19 CAR T-Cell Therapy for Refractory Ulcerative Colitis, Gastroenterology, in press.","DOI":"10.1053\/j.gastro.2025.11.013"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.cbi.2013.12.007","article-title":"Celastrol Ameliorates Murine Colitis via Modulating Oxidative Stress, Inflammatory Cytokines and Intestinal Homeostasis","volume":"210","author":"Shaker","year":"2014","journal-title":"Chem.-Biol. Interact."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.lfs.2012.07.032","article-title":"Beta-Catenin Mediates the Apoptosis Induction Effect of Celastrol in HT29 Cells","volume":"91","author":"Lu","year":"2012","journal-title":"Life Sci."},{"key":"ref_235","doi-asserted-by":"crossref","unstructured":"Lin, L., Sun, Y., Wang, D., Zheng, S., Zhang, J., and Zheng, C. (2016). Celastrol Ameliorates Ulcerative Colitis-Related Colorectal Cancer in Mice via Suppressing Inflammatory Responses and Epithelial-Mesenchymal Transition. Front. Pharmacol., 6.","DOI":"10.3389\/fphar.2015.00320"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1158\/1535-7163.MCT-09-0304","article-title":"Silibinin Suppresses Growth and Induces Apoptotic Death of Human Colorectal Carcinoma LoVo Cells in Culture and Tumor Xenograft","volume":"8","author":"Kaur","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"1562010","DOI":"10.1155\/2018\/1562010","article-title":"Chemopreventive Effects of Silibinin on Colitis-Associated Tumorigenesis by Inhibiting IL-6\/STAT3 Signaling Pathway","volume":"2018","author":"Zheng","year":"2018","journal-title":"Mediat. Inflamm."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1093\/ibd\/izz007","article-title":"Silibinin Retards Colitis-Associated Carcinogenesis by Repression of Cdc25C in Mouse Model","volume":"25","author":"Li","year":"2019","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"972","DOI":"10.4161\/auto.28374","article-title":"Small Molecule-Driven Mitophagy-Mediated NLRP3 Inflammasome Inhibition Is Responsible for the Prevention of Colitis-Associated Cancer","volume":"10","author":"Guo","year":"2014","journal-title":"Autophagy"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1016\/j.cgh.2017.02.029","article-title":"Endoscopic and Histologic Healing in Children with Inflammatory Bowel Diseases Treated with Thalidomide","volume":"15","author":"Lazzerini","year":"2017","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"3803","DOI":"10.1007\/s10620-021-07067-2","article-title":"Thalidomide Attenuates Colitis and Is Associated with the Suppression of M1 Macrophage Polarization by Targeting the Transcription Factor IRF5","volume":"66","author":"Lu","year":"2021","journal-title":"Dig. Dis. Sci."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"7458","DOI":"10.7150\/thno.38081","article-title":"Orally Deliverable Nanotherapeutics for the Synergistic Treatment of Colitis-Associated Colorectal Cancer","volume":"9","author":"Han","year":"2019","journal-title":"Theranostics"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.bcp.2017.02.021","article-title":"Mechanisms of Colitis-Accelerated Colon Carcinogenesis and Its Prevention with the Combination of Aspirin and Curcumin: Transcriptomic Analysis Using RNA-Seq","volume":"135","author":"Guo","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1093\/carcin\/bgy043","article-title":"DNA Methylome and Transcriptome Alterations and Cancer Prevention by Curcumin in Colitis-Accelerated Colon Cancer in Mice","volume":"39","author":"Guo","year":"2018","journal-title":"Carcinogenesis"},{"key":"ref_245","doi-asserted-by":"crossref","unstructured":"Robinson, P., Italia, Z., Italia, Z., Hoang, T., Rodriguez, E., Eckols, T.K., Kasembeli, M., Zorrilla, L.H., Soto, L.M.S., and Mahalingam, R. (2025). STAT3 Inhibition to Treat Ulcerative Colitis-Associated Colorectal Cancer. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262110808"},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"808","DOI":"10.24976\/Discov.Med.202537196.71","article-title":"Adjuvant Immunotherapy in Microsatellite Instability-High Colon Cancer: A Literature Review on Efficacy, Challenges, and Future Directions","volume":"37","author":"Karri","year":"2025","journal-title":"Discov. Med."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"e100106","DOI":"10.1136\/egastro-2024-100106","article-title":"Immunotherapy against Colorectal Cancer via Delivery of Anti-PD-L1 Nanobody mRNA","volume":"3","author":"Chu","year":"2025","journal-title":"eGastroenterology"},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"113365","DOI":"10.1016\/j.intimp.2024.113365","article-title":"A Comprehensive Review of Immune Checkpoint Inhibitors for Cancer Treatment","volume":"143","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1053\/j.gastro.2009.08.062","article-title":"Inhibition of Colon Carcinogenesis by 2-Methoxy-5-Amino-N-Hydroxybenzamide, a Novel Derivative of Mesalamine","volume":"138","author":"Stolfi","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.3390\/cimb45040189","article-title":"Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation","volume":"45","author":"Wang","year":"2023","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12929-025-01208-9","article-title":"Microbiome Modulation of Tumorigenesis and Immune Responses","volume":"33","author":"Chen","year":"2026","journal-title":"J. Biomed. Sci."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"114867","DOI":"10.1016\/j.yexcr.2025.114867","article-title":"Metabolic Adaptation in Colorectal Cancer Microenvironment: Focus on Cancer-Associated Fibroblasts (CAFs) and Tumor-Associated Macrophages (TAMs)","volume":"455","author":"Hsu","year":"2026","journal-title":"Exp. Cell Res."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"218016","DOI":"10.1016\/j.canlet.2025.218016","article-title":"Polyamines in Pancreatic Cancer: Reshaping the Immunosuppressive Tumor Microenvironment","volume":"633","author":"Jiang","year":"2025","journal-title":"Cancer Lett."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1080\/07357907.2025.2594741","article-title":"Prognostic Model Based on NAD+ Metabolism-Related Genes Predicts Breast Cancer Outcomes and Guides Immunotherapy","volume":"44","author":"Wang","year":"2026","journal-title":"Cancer Investig."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13072-025-00575-9","article-title":"Crosstalk between Metabolism and Epigenetics during Macrophage Polarization","volume":"18","author":"Zhang","year":"2025","journal-title":"Epigenet. Chromatin"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/s41419-025-08357-7","article-title":"Hypoxic Tumor Exosomes Suppress Macrophage Inflammation and Ferroptosis via NDUFV2 to Enhance Bystander Tumor Radioresistance","volume":"17","author":"Zhang","year":"2025","journal-title":"Cell Death Dis."},{"key":"ref_257","doi-asserted-by":"crossref","unstructured":"O\u2019Connor, G., Hazime, H., Burgue\u00f1o, J.F., Fern\u00e1ndez, I., Santander, A.M., Brito, N., Faust, K.M., Ban, Y., Quintero, M.A., and Deo, S.K. (Gastroenterology, 2026). Quorum-Sensing Molecules Are Elevated in Long-Standing Ulcerative Colitis and Are Linked to the Development of Colitis-Associated Cancer, Gastroenterology, in press.","DOI":"10.1053\/j.gastro.2026.01.023"},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"2597626","DOI":"10.1080\/19490976.2025.2597626","article-title":"Microbial Metabolite Trimethylamine-N-Oxide Facilitates Colorectal Inflammation-Cancer Transformation by Blocking Lysosomal Degradation of Wnt Signaling","volume":"17","author":"Yang","year":"2025","journal-title":"Gut Microbes"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/8\/1230\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T04:11:42Z","timestamp":1777263102000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/8\/1230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,13]]},"references-count":258,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["cancers18081230"],"URL":"https:\/\/doi.org\/10.3390\/cancers18081230","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,13]]}}}