Preexisting ulcerative colitis increases the risk of immune-related colitis and predicts divergent survival outcomes in gastrointestinal cancer patients treated with immune checkpoint inhibitors

BackgroundThe risk of immune-related colitis (IRC) and efficacy of immune checkpoint inhibitors (ICIs) in patients with gastrointestinal cancers and preexisting ulcerative colitis (UC) has not been well described.Patients and methodsWe divided the patients with gastrointestinal cancers and preexisti...

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Main Authors: Shuo Xu, Lu Chen, Kaixuan Liu, Hui Tao, Zhengzheng Ji, Jiamin Wu, Yuanyi Zhao, Qiankun Zhou, Liuying Li, Hanlong Zhu, Yunzhe Wang, Fangyu Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1627680/full
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author Shuo Xu
Lu Chen
Kaixuan Liu
Hui Tao
Zhengzheng Ji
Jiamin Wu
Yuanyi Zhao
Qiankun Zhou
Liuying Li
Hanlong Zhu
Yunzhe Wang
Fangyu Wang
author_facet Shuo Xu
Lu Chen
Kaixuan Liu
Hui Tao
Zhengzheng Ji
Jiamin Wu
Yuanyi Zhao
Qiankun Zhou
Liuying Li
Hanlong Zhu
Yunzhe Wang
Fangyu Wang
author_sort Shuo Xu
collection DOAJ
description BackgroundThe risk of immune-related colitis (IRC) and efficacy of immune checkpoint inhibitors (ICIs) in patients with gastrointestinal cancers and preexisting ulcerative colitis (UC) has not been well described.Patients and methodsWe divided the patients with gastrointestinal cancers and preexisting UC who received ICIs between January 2021 and May 2024 into two groups as IRC group and non-IRC group. The electronic medical records were reviewed to compare the risk of IRC between two groups. Survival analysis and COX regression was conducted to assess clinical efficacy.ResultsOf the 138 patients in study, 31 patients had a history of UC prior to initiation of immunotherapy. IRC occurred in 22 patients (71.0%) and over half experienced severe IRC (54.5%), a rate higher than that among similar patients without underlying UC (17.4%, p = 0.013). Compared with patients without UC who did not experience IRC, PFS and OS of patients with UC who had mild IRC were longer (PFS: 170 vs 96 days, p < 0.001; OS: 261 vs 172 days, p = 0.021) and those with severe IRC demonstrated merely a marginal advantage in terms of PFS (147 vs 96 days, p = 0.001), but no significant difference was observed in OS (171 vs 172 days, p = 0.851). The Multivariate analysis affirmed that mild IRC were correlated with a favorable prognosis (HR = 0.286, 95%CI: 0.106-0.769, p = 0.013), whereas severe IRC was not sufficient to be recognized as independent risk factors affecting survival outcomes. (HR = 1.149, 95%CI: 0.502-2.633, p = 0.742). The result of serum cytokines showed that the levels of IL-6 and IL-17A in patients with IRC were significantly elevated.ConclusionFor preexisting UC patients treated with ICIs, the risk of IRC is increased. Mild IRC may suggest a favorable prognosis, and being vigilant and effectively managing the occurrence of severe IRC is crucial for maximizing clinical benefits. Targeting the IL-6 pathway may be a potential new strategy for treating IRC in the future.
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spelling doaj-art-073fe4509e3c457f9f910d2df8cd77fc2025-08-20T03:37:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16276801627680Preexisting ulcerative colitis increases the risk of immune-related colitis and predicts divergent survival outcomes in gastrointestinal cancer patients treated with immune checkpoint inhibitorsShuo Xu0Lu Chen1Kaixuan Liu2Hui Tao3Zhengzheng Ji4Jiamin Wu5Yuanyi Zhao6Qiankun Zhou7Liuying Li8Hanlong Zhu9Yunzhe Wang10Fangyu Wang11Department of Gastroenterology and Hepatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, ChinaDepartment of Gastroenterology and Hepatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, ChinaDepartment of Gastroenterology and Hepatology, Cangzhou People’s Hospital, Cangzhou, Hebei, ChinaDepartment of Gastroenterology and Hepatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, ChinaDepartment of Rheumatology and Immunology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Gastroenterology and Hepatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, ChinaDepartment of Gastroenterology, Jinling Hospital, Nanjing Medical University, Nanjing, ChinaDepartment of Gastroenterology and Hepatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, ChinaDepartment of Gastroenterology and Hepatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, ChinaDepartment of Gastroenterology and Hepatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, ChinaDepartment of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Gastroenterology and Hepatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, ChinaBackgroundThe risk of immune-related colitis (IRC) and efficacy of immune checkpoint inhibitors (ICIs) in patients with gastrointestinal cancers and preexisting ulcerative colitis (UC) has not been well described.Patients and methodsWe divided the patients with gastrointestinal cancers and preexisting UC who received ICIs between January 2021 and May 2024 into two groups as IRC group and non-IRC group. The electronic medical records were reviewed to compare the risk of IRC between two groups. Survival analysis and COX regression was conducted to assess clinical efficacy.ResultsOf the 138 patients in study, 31 patients had a history of UC prior to initiation of immunotherapy. IRC occurred in 22 patients (71.0%) and over half experienced severe IRC (54.5%), a rate higher than that among similar patients without underlying UC (17.4%, p = 0.013). Compared with patients without UC who did not experience IRC, PFS and OS of patients with UC who had mild IRC were longer (PFS: 170 vs 96 days, p < 0.001; OS: 261 vs 172 days, p = 0.021) and those with severe IRC demonstrated merely a marginal advantage in terms of PFS (147 vs 96 days, p = 0.001), but no significant difference was observed in OS (171 vs 172 days, p = 0.851). The Multivariate analysis affirmed that mild IRC were correlated with a favorable prognosis (HR = 0.286, 95%CI: 0.106-0.769, p = 0.013), whereas severe IRC was not sufficient to be recognized as independent risk factors affecting survival outcomes. (HR = 1.149, 95%CI: 0.502-2.633, p = 0.742). The result of serum cytokines showed that the levels of IL-6 and IL-17A in patients with IRC were significantly elevated.ConclusionFor preexisting UC patients treated with ICIs, the risk of IRC is increased. Mild IRC may suggest a favorable prognosis, and being vigilant and effectively managing the occurrence of severe IRC is crucial for maximizing clinical benefits. Targeting the IL-6 pathway may be a potential new strategy for treating IRC in the future.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1627680/fullimmune checkpoint inhibitorsulcerative colitisimmune-related colitisgastrointestinal cancerssurvival outcomes
spellingShingle Shuo Xu
Lu Chen
Kaixuan Liu
Hui Tao
Zhengzheng Ji
Jiamin Wu
Yuanyi Zhao
Qiankun Zhou
Liuying Li
Hanlong Zhu
Yunzhe Wang
Fangyu Wang
Preexisting ulcerative colitis increases the risk of immune-related colitis and predicts divergent survival outcomes in gastrointestinal cancer patients treated with immune checkpoint inhibitors
Frontiers in Immunology
immune checkpoint inhibitors
ulcerative colitis
immune-related colitis
gastrointestinal cancers
survival outcomes
title Preexisting ulcerative colitis increases the risk of immune-related colitis and predicts divergent survival outcomes in gastrointestinal cancer patients treated with immune checkpoint inhibitors
title_full Preexisting ulcerative colitis increases the risk of immune-related colitis and predicts divergent survival outcomes in gastrointestinal cancer patients treated with immune checkpoint inhibitors
title_fullStr Preexisting ulcerative colitis increases the risk of immune-related colitis and predicts divergent survival outcomes in gastrointestinal cancer patients treated with immune checkpoint inhibitors
title_full_unstemmed Preexisting ulcerative colitis increases the risk of immune-related colitis and predicts divergent survival outcomes in gastrointestinal cancer patients treated with immune checkpoint inhibitors
title_short Preexisting ulcerative colitis increases the risk of immune-related colitis and predicts divergent survival outcomes in gastrointestinal cancer patients treated with immune checkpoint inhibitors
title_sort preexisting ulcerative colitis increases the risk of immune related colitis and predicts divergent survival outcomes in gastrointestinal cancer patients treated with immune checkpoint inhibitors
topic immune checkpoint inhibitors
ulcerative colitis
immune-related colitis
gastrointestinal cancers
survival outcomes
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1627680/full
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