Li Huibo, Pan Yumiao, Liu Wenzheng, Zhang Hejun, Tian Xueli, Zhao Rongsheng, Zhu Yi Zhun
Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China.
State Key Laboratory of Quality Research in Chinese Medicine, School of Pharmacy, Macau University of Science and Technology, Macau SAR 999078, China.
Pharmaceuticals (Basel). 2025 Aug 15;18(8):1211. doi: 10.3390/ph18081211.
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy by providing durable responses and a favorable safety profile, ushering in a new era of tumor immunotherapy. However, immune-related adverse events (irAEs) remain a significant clinical challenge. Among these, gastrointestinal irAEs, especially immune-related colitis (ir-colitis), can lead to serious complications if not promptly recognized and managed. Here, we present a case of grade 3 ir-colitis induced by the programmed cell death protein 1 (PD-1) inhibitor sintilimab in a 68-year-old woman with endometrial cancer. The patient developed severe acute diarrhea following ICI administration, which progressed despite initial antidiarrheal and antimicrobial treatments. A multidisciplinary team (MDT) involving gastroenterologists, oncologists, a pathologist, and a clinical pharmacist confirmed the diagnosis and implemented high-dose corticosteroid therapy, yielding significant clinical improvement. Importantly, this report highlights the mechanistic link between PD-1 blockade and ir-colitis pathogenesis, focusing on the dysregulation of the mucosal immune environment and its role in triggering colonic injury. In addition to the case description, we provide a comprehensive review of the literature and clinical guidelines, discussing risk factors, diagnostic approaches, therapeutic strategies, and long-term monitoring. By integrating insights from pharmacology, immunology, and clinical practice, this work emphasizes the importance of early detection, patient education, and MDT collaboration for optimizing therapeutic outcomes and advancing the understanding of ir-colitis in the context of ICI therapy.
免疫检查点抑制剂(ICIs)通过提供持久疗效和良好的安全性,彻底改变了癌症治疗方式,开创了肿瘤免疫治疗的新时代。然而,免疫相关不良事件(irAEs)仍然是一项重大的临床挑战。其中,胃肠道irAEs,尤其是免疫相关结肠炎(ir-结肠炎),如果不能及时识别和处理,可能会导致严重并发症。在此,我们报告一例68岁子宫内膜癌女性患者,由程序性细胞死亡蛋白1(PD-1)抑制剂信迪利单抗诱发的3级ir-结肠炎。患者在接受ICI治疗后出现严重急性腹泻,尽管最初进行了止泻和抗菌治疗,但仍持续进展。一个由胃肠病学家、肿瘤学家、病理学家和临床药师组成的多学科团队(MDT)确诊了病情,并实施了高剂量皮质类固醇治疗,临床症状得到显著改善。重要的是,本报告强调了PD-1阻断与ir-结肠炎发病机制之间的机制联系,重点关注黏膜免疫环境的失调及其在引发结肠损伤中的作用。除了病例描述外,我们还对文献和临床指南进行了全面综述,讨论了危险因素、诊断方法、治疗策略和长期监测。通过整合药理学、免疫学和临床实践的见解,这项工作强调了早期检测、患者教育和MDT协作对于优化治疗结果以及推进对ICI治疗背景下ir-结肠炎理解的重要性。