Markovic Marina, Niciforovic Danijela, Mladenovic Violeta, Pavlovic Dragica, Papic Dragana, Milojevic Katarina, Jovanovic Dalibor, Spasojevic Marija, Milic Rade
Center for Internal Oncology, University Clinical Center Kragujevac, Kragujevac, Serbia.
Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
Int J Immunopathol Pharmacol. 2025 Jan-Dec;39:3946320251326699. doi: 10.1177/03946320251326699. Epub 2025 Apr 15.
Immune Checkpoint Inhibitors (ICIs) are monoclonal antibodies that block inhibitory immune targets, such as cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed death ligand 1 (PD-L). Pembrolizumab targets the PD-1 receptor of lymphocytes in lung cancer treatment. ICI checkpoint blockade enhances immunity against cancer cells. However, loss of immunoregulatory control can cause autoimmune reactions in various organs, leading to immune-related adverse events (irAEs). The most common irAE is ICIs-induced colitis, which usually develops 6-8 weeks after ICI initiation and can involve any part of the gastrointestinal system. Herein, we report a presentation of pembrolizumab-induced colitis in a female patient with metastatic lung cancer and review the most recent findings in the model of checkpoint-induced colitis. It was interesting to learn that the colon mucosa may show normal macroscopic findings, but microscopically, immunotherapy-induced autoimmune colitis could be present. Additionally, patients with grade 2 or higher symptoms should have a colonoscopy, receive systemic corticosteroids as treatment, and, based on their response, receive biologic therapy. Here, we present a case report of in a 45-year-old female who has been a smoker for 25 years, without comorbidities, and with metastatic lung cancer who developed colitis after the seventh cycle of pembrolizumab. This case presentation highlights the importance of early recognition and appropriate intervention in order to prevent permanent interruption of treatment with checkpoint inhibitors, as well as prevention of colitis complications.
免疫检查点抑制剂(ICIs)是一类单克隆抗体,可阻断抑制性免疫靶点,如细胞毒性T淋巴细胞相关抗原4(CTLA-4)、程序性细胞死亡蛋白1(PD-1)和程序性死亡配体1(PD-L)。帕博利珠单抗在肺癌治疗中靶向淋巴细胞的PD-1受体。ICI检查点阻断可增强对癌细胞的免疫力。然而,免疫调节控制的丧失可导致各器官发生自身免疫反应,引发免疫相关不良事件(irAEs)。最常见的irAE是ICI诱导的结肠炎,通常在开始使用ICI后6-8周出现,可累及胃肠道系统的任何部位。在此,我们报告一例转移性肺癌女性患者发生帕博利珠单抗诱导的结肠炎病例,并综述检查点诱导性结肠炎模型的最新研究结果。有趣的是,结肠黏膜在宏观上可能表现正常,但在微观上可能存在免疫治疗诱导的自身免疫性结肠炎。此外,出现2级或更高症状的患者应接受结肠镜检查,接受全身糖皮质激素治疗,并根据其反应接受生物治疗。在此,我们报告一例45岁女性病例,该患者有25年吸烟史,无合并症,患有转移性肺癌,在接受第七周期帕博利珠单抗治疗后发生结肠炎。本病例报告强调了早期识别和适当干预的重要性,以防止检查点抑制剂治疗的永久中断以及预防结肠炎并发症。