{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T06:24:03Z","timestamp":1787207043178,"version":"build-2736575974"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013302","name":"King Abdullah International Medical Research Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013302","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Immune checkpoint inhibitors (ICIs) have become the standard-of-care in various cancer types. However, treatment with ICIs occasionally cause immune-related adverse events (irAEs). This study assessed the incidence and clinical features of irAEs and examined their association with treatment outcomes in patients with solid tumors receiving ICIs. We conducted a retrospective cohort study including 385 patients with histologically confirmed solid tumors treated with ICIs. Patients were categorized according to the occurrence of irAEs. Baseline clinicopathological characteristics, irAE patterns, management strategies, and survival outcomes were analysed. To minimize immortal time bias, landmark analyses at three months were performed. Multivariable Cox regression models were used to evaluate the association between irAEs occurring within the first three months of treatment and subsequent survival outcomes after adjustment for clinically relevant confounders. Among 385 patients, 181 (47%) developed at least one irAE during ICI treatment. The most frequently observed irAEs included transaminitis, thyroiditis, pneumonitis, rash, and colitis. Patients who developed irAEs had significantly improved survival outcomes compared with those without irAEs. In landmark Kaplan\u2013Meier analyses, patients who developed irAEs during follow-up had significantly improved OS and PFS compared with those who did not. In landmark-adjusted multivariable analysis, irAEs was associated with improved OS (HR 0.673, 95% CI 0.453\u20131.00; P\u00a0=\u00a00.0498), whereas the association with PFS was not statistically significant (HR 0.851, 95% CI 0.630\u20131.149; P\u00a0=\u00a00.2916). A baseline neutrophil-to-lymphocyte ratio (NLR) &amp;lt;3 was associated with favourable survival outcomes. Most irAEs were managed with corticosteroids and temporary treatment interruption. Development of irAEs was associated with improved survival outcomes in patients with solid tumors treated with ICIs. These findings support the hypothesis that irAEs was associated with enhanced anti-tumor immune activity. Real-world characterization of irAEs and their management may help optimize patient monitoring and treatment strategies during immunotherapy.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1910109","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T05:29:03Z","timestamp":1787203743000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of immune-related adverse events is associated with improved survival outcomes in cancer patients receiving immune checkpoint inhibitors"],"prefix":"10.3389","volume":"17","author":[{"given":"Faizah M.","family":"Alotaibi","sequence":"first","affiliation":[{"name":"College of Science and Health Professions, King Saud bin Abdulaziz for Health Science","place":["Riyadh, Saudi Arabia"]},{"name":"King Abdullah International Medical Research Center","place":["Al-Ahsa, Saudi Arabia"]},{"name":"Ministry of National Guard Health Affairs","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seham A.","family":"Khashwayn","sequence":"additional","affiliation":[{"name":"College of Science and Health Professions, King Saud bin Abdulaziz for Health Science","place":["Riyadh, Saudi Arabia"]},{"name":"King Abdullah International Medical Research Center","place":["Al-Ahsa, Saudi Arabia"]},{"name":"Ministry of National Guard Health Affairs","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamia K.","family":"Alshamlani","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud Bin Abdulaziz for Health Science","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayan A.","family":"Almutairi","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud Bin Abdulaziz for Health Science","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anas K.","family":"Alghamdi","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud Bin Abdulaziz for Health Science","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nawaf M.","family":"Alamer","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud Bin Abdulaziz for Health Science","place":["Riyadh, Saudi Arabia"]},{"name":"Emergency Medicine, King Fahad Medical City","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohannad A.","family":"Alghamdi","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud Bin Abdulaziz for Health Science","place":["Riyadh, Saudi Arabia"]},{"name":"Internal Medicine, Department of Medicine, King Faisal Specialized Hospital and Research Center","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Badi A.","family":"Alotaibi","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center","place":["Al-Ahsa, Saudi Arabia"]},{"name":"Ministry of National Guard Health Affairs","place":["Riyadh, Saudi Arabia"]},{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanan","family":"Alshammari","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center","place":["Al-Ahsa, Saudi Arabia"]},{"name":"Ministry of National Guard Health Affairs","place":["Riyadh, Saudi Arabia"]},{"name":"Department of Oncology, Ministry of National Guard Health Affairs","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.20892\/j.issn.2095-3941.2024.0055","article-title":"Immune checkpoint inhibitors: breakthroughs in cancer treatment","volume":"21","author":"Kong","year":"2024","journal-title":"Cancer Biol Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12030738","article-title":"Review of indications of FDA-approved immune checkpoint inhibitors per NCCN guidelines with the level of evidence","volume":"12","author":"Vaddepally","year":"2020","journal-title":"Cancers"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00311","article-title":"Current diagnosis and management of immune related adverse events (irAEs) induced by immune checkpoint inhibitor therapy","volume":"8","author":"Kumar","year":"2017","journal-title":"Front Pharmacol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"38","DOI":"10.7326\/aitc202402200","article-title":"Immune-related adverse events of checkpoint inhibitors","volume":"6","author":"Ramos-Casals","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"B5","doi-asserted-by":"publisher","first-page":"65","DOI":"10.17998\/jlc.2025.12.21","article-title":"Immune-related adverse events in hepatocellular carcinoma: organ-specific patterns and management approaches","volume":"26","author":"Choi","year":"2025","journal-title":"J Liver Cancer"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2020.7567","article-title":"Multiorgan immune-related adverse events during treatment with atezolizumab","volume":"18","author":"Kichenadasse","year":"2020","journal-title":"J Natl Compr Cancer Network"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2022.01.001","article-title":"Immune-related adverse events in various organs caused by immune checkpoint inhibitors","volume":"71","author":"Okiyama","year":"2022","journal-title":"Allergol Int"},{"key":"B8","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s10238-026-02052-3","article-title":"Clinical characteristics and therapies of multi-organ immune related adverse events","volume":"26","author":"Wang","year":"2026","journal-title":"Clin Exp Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1200\/jco.21.01440","article-title":"Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update","volume":"39","author":"Schneider","year":"2021","journal-title":"J Clin Oncol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1007\/s00262-024-03852-w","article-title":"Biomarker role of thyroid irAE and PD-L1 positivity in predicting PD-1 blockade efficacy in patients with non-small cell lung cancer","volume":"73","author":"Kim","year":"2024","journal-title":"Cancer Immunol Immunother"},{"key":"B11","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.iac.2025.01.010","article-title":"The current and future of biomarkers of immune related adverse effects (irAE)","volume":"50","author":"Bracamonte-Baran","year":"2024","journal-title":"Rheumatic Dis Clinics North America"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-026-46185-7","article-title":"Association of immune-related adverse events with survival in patients receiving immune checkpoint inhibitor plus chemotherapy for lung cancer","author":"Takada","year":"2026","journal-title":"Sci Rep"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/1759-7714.70261","article-title":"Association of immune\u2010related adverse events and the efficacy of immune checkpoint inhibitors in non\u2010small cell lung cancer: Adjusting for immortal time bias","volume":"17","author":"Kuwabara","year":"2026","journal-title":"Thorac Cancer"},{"key":"B14","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1186\/s12916-020-01549-2","article-title":"Are immune-related adverse events associated with the efficacy of immune checkpoint inhibitors in patients with cancer? A systematic review and meta-analysis","volume":"18","author":"Zhou","year":"2020","journal-title":"BMC Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.633032","article-title":"Association of immune related adverse events with efficacy of immune checkpoint inhibitors and overall survival in cancers: a systemic review and meta-analysis","volume":"11","author":"Fan","year":"2021","journal-title":"Front Oncol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-024-03798-6","article-title":"The role of tumor types in immune-related adverse events","volume":"27","author":"Xu","year":"2025","journal-title":"Clin Transl Oncol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-020-02797-0","article-title":"Genetic determinants of immune-related adverse events in patients with melanoma receiving immune checkpoint inhibitors","volume":"70","author":"Abdel-Wahab","year":"2021","journal-title":"Cancer Immunol Immunother"},{"key":"B18","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s13073-019-0652-8","article-title":"Mechanisms of immune-related adverse events associated with immune checkpoint blockade: using germline genetics to develop a personalized approach","volume":"11","author":"Khan","year":"2019","journal-title":"Genome Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"86","DOI":"10.3322\/caac.21596","article-title":"A review of cancer immunotherapy toxicity","volume":"70","author":"Kennedy","year":"2020","journal-title":"CA: A Cancer J For Clin"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/ajco.13332","article-title":"The role of immunosuppressive agents in the management of severe and refractory immune\u2010related adverse events","volume":"16","author":"Wang","year":"2020","journal-title":"Asia\u2010Pacific J Clin Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1200\/jco.24.00191","article-title":"Corticosteroids for immune-related adverse events and checkpoint inhibitor efficacy: analysis of six clinical trials","volume":"42","author":"Verheijden","year":"2024","journal-title":"J Clin Oncol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2015.60.8448","article-title":"Immune-related adverse events, need for systemic immunosuppression, and effects on survival and time to treatment failure in patients with melanoma treated with ipilimumab at Memorial Sloan Kettering Cancer Center","volume":"33","author":"Horvat","year":"2015","journal-title":"J Clin Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.9151","article-title":"Immortal time bias in observational studies","volume":"325","author":"Yadav","year":"2021","journal-title":"JAMA"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0218-0","article-title":"Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance","volume":"16","author":"Martins","year":"2019","journal-title":"Nat Rev Clin Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.2105\/ajph.2021.306590","article-title":"Lack of Arab or Middle Eastern and North African health data undermines assessment of health disparities","volume":"112","author":"Awad","year":"2022","journal-title":"Am J Public Health"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.21037\/tlcr-24-299","article-title":"Prognostic relevance of immune-related adverse events in lung cancer patients undergoing immune checkpoint inhibitor therapy: a systematic review and meta-analysis","volume":"13","author":"Huang","year":"2024","journal-title":"Trans Lung Cancer Res"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2020.102134","article-title":"Association between immune-related side effects and efficacy and benefit of immune checkpoint inhibitors\u2013a systematic review and meta-analysis","volume":"92","author":"Hussaini","year":"2021","journal-title":"Cancer Treat Rev"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrc.2016.07.017","article-title":"Immortal time bias in observational studies of time-to-event outcomes","volume":"36","author":"Jones","year":"2016","journal-title":"J Crit Care"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2013.03.010","article-title":"The systemic inflammation-based neutrophil\u2013lymphocyte ratio: experience in patients with cancer","volume":"88","author":"Guthrie","year":"2013","journal-title":"Crit Rev Oncology\/Hematol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dju124","article-title":"Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis","volume":"106","author":"Templeton","year":"2014","journal-title":"J Natl Cancer Institute"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0222-4","article-title":"Tumour-associated neutrophils in patients with cancer","volume":"16","author":"Shaul","year":"2019","journal-title":"Nat Rev Clin Oncol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.52","article-title":"Neutrophils in cancer: neutral no more","volume":"16","author":"Coffelt","year":"2016","journal-title":"Nat Rev Cancer"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1482746","article-title":"Prognostic value of inflammatory markers NLR, PLR, LMR, dNLR, ANC in melanoma patients treated with immune checkpoint inhibitors: a meta-analysis and systematic review","volume":"15","author":"Ou","year":"2024","journal-title":"Front Immunol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/s41416-024-02887-1","article-title":"Cancer and treatment specific incidence rates of immune-related adverse events induced by immune checkpoint inhibitors: a systematic review","volume":"132","author":"Jayathilaka","year":"2024","journal-title":"Br J Cancer"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1200\/jop.18.00005","article-title":"Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline","volume":"36","author":"Brahmer","year":"2018","journal-title":"J Clin Oncol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1080\/1750743x.2026.2616478","article-title":"Dual-edged therapy: corticosteroids in the era of immunotherapy","author":"Lim","year":"2025","journal-title":"Taylor Francis"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1200\/jco.19.00189","article-title":"Immune checkpoint inhibitor outcomes for patients with non\u2013small-cell lung cancer receiving baseline corticosteroids for palliative versus nonpalliative indications","volume":"37","author":"Ricciuti","year":"2019","journal-title":"J Clin Oncol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2018.79.0006","article-title":"Impact of baseline steroids on efficacy of programmed cell death-1 and programmed death-ligand 1 blockade in patients with non\u2013small-cell lung cancer","volume":"36","author":"Arbour","year":"2018","journal-title":"J Clin Oncol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1910109\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T05:29:04Z","timestamp":1787203744000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1910109\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":38,"alternative-id":["10.3389\/fimmu.2026.1910109"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1910109","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]},"article-number":"1910109"}}