170419 20260420103355.0 doi 10.3390/gastroent17010020 sideral 148879 ART-2026-148879 eng Polo Cuadro, Cristina Immune-mediated colitis in the era of immune checkpoint inhibition: from mechanisms to clinical management 2026 Immunotherapy with immune checkpoint inhibitors (ICIs) has represented a major breakthrough in the treatment of multiple solid and hematological malignancies, significantly improving survival and tumor control. However, the blockade of immune regulatory pathways such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) is associated with the development of immune-related adverse events, among which immune-mediated colitis (IMC) constitutes one of the most relevant gastrointestinal complications due to its frequency, potential severity, and impact on the continuation of oncologic treatment. IMC typically presents with diarrhea, abdominal pain, and gastrointestinal bleeding, and may progress to severe, life-threatening forms. Its incidence varies according to the type of ICI, and is higher with CTLA-4 inhibitors and particularly elevated with combination therapies. The pathophysiology is complex and multifactorial, involving dysregulated activation of proinflammatory T lymphocytes, impairment of immune regulatory mechanisms, disruption of the intestinal epithelial barrier, and a key modulatory role of the gut microbiota. Diagnosis requires a high index of clinical suspicion and relies on endoscopy with biopsies, given the poor correlation between clinical severity and endoscopic or histological findings. Fecal biomarkers, such as calprotectin and lactoferrin, are useful for risk stratification and disease monitoring. Treatment is based on a stepwise immunosuppressive approach, with corticosteroids as first-line therapy and biologic agents such as infliximab or vedolizumab in refractory cases. Emerging strategies, including fecal microbiota transplantation, offer new therapeutic perspectives. This article provides a comprehensive review of the current evidence on the epidemiology, pathophysiology, diagnosis, and management of IMC, as well as future challenges and opportunities in its clinical management. Access copy available to the general public Unrestricted info:eu-repo/grantAgreement/ES/ISCIII JR24-00033 info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Corsino Roche, Pilar Gascón Ruiz, Marta Universidad de Zaragoza (orcid)0000-0002-6811-6654 García López, Santiago Universidad de Zaragoza (orcid)0000-0003-3970-5457 Yagüe Caballero, Carmen Royo Esteban, Ana Almenara Michelena, Laura Casas Deza, Diego (orcid)0000-0001-6883-8940 1007 610 Universidad de Zaragoza Dpto. Medicina, Psiqu. y Derm. Area Medicina 17, 20 (2026), 23 Gastroenterology Insights 2036-7422 1268588 http://zaguan.unizar.es/record/170419/files/texto_completo.pdf Versión publicada 2543933 http://zaguan.unizar.es/record/170419/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:170419 articulos driver 2026-04-18-10:49:13 ARTICLE