Kim Min Kyu, Son Hye-Nam, Hong Seung Wook, Park Sang Hyoung, Yang Dong-Hoon, Ye Byong Duk, Byeon Jeong-Sik, Myung Seung-Jae, Yang Suk-Kyun, Yoon Shinkyo, Hwang Sung Wook
Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Therap Adv Gastroenterol. 2024 Dec 23;17:17562848241309445. doi: 10.1177/17562848241309445. eCollection 2024.
Immune checkpoint inhibitor (ICI)-induced colitis is a significant adverse event associated with ICI therapy, known to be linked to increased cytotoxic T-cell activity.
To compare T-cell subsets based on the endoscopic features of ICI-induced colitis and to compare these findings with those of inflammatory bowel disease (IBD).
Prospective cohort study.
We analyzed patients with ICI-induced colitis, confirmed through both endoscopic and histological evaluation. Biopsy specimens were examined using multiplex immunohistochemistry to assess their immune cell profile. Clinical outcomes were analyzed. Immune cell profiles were compared based on their endoscopic features and contrasted with those of patients with IBD.
Seventeen patients with ICI-induced colitis were included in the study. All patients showed clinical improvement after treatment, and steroids were administered to 11 patients (64.7%). Based on endoscopic features, the patients were classified as Crohn's disease (CD)-like ( = 3, 17.6%), ulcerative colitis (UC)-like ( = 9, 52.9%), or microscopic colitis (MC)-like ( = 5, 29.4%). In ICI-induced colitis, cytotoxic T cells (Tc cells) were more predominant than helper T cells (Th cells) ( = 0.053), and this trend was most pronounced in the MC-like subtype ( = 0.020). When comparing the number of CD8+ cells infiltrating the crypts, both the UC-like and MC-like subtypes had significantly more infiltrating cells than the CD-like subtype ( = 0.008 and = 0.016, respectively). In comparison to IBD, IBD exhibited a Th-dominant profile, whereas CD-like ICI-induced colitis had a lower Th cell density than CD ( = 0.032) and UC-like ICI-induced colitis had a higher Tc density than UC ( = 0.045).
Analysis of T-cell subsets of ICI-induced colitis revealed a Tc-dominant profile, contrasting with the Th dominance observed in patients with IBD. The Tc-dominant profile was evident in UC-like and MC-like subtypes, with significant crypt infiltration by CD8+ cells. Tc may play an important role in the pathophysiology of ICI-induced colitis.
免疫检查点抑制剂（ICI）诱导的结肠炎是与ICI治疗相关的一种重要不良事件，已知与细胞毒性T细胞活性增加有关。
根据ICI诱导的结肠炎的内镜特征比较T细胞亚群，并将这些结果与炎症性肠病（IBD）的结果进行比较。
前瞻性队列研究。
我们分析了经内镜和组织学评估确诊的ICI诱导的结肠炎患者。使用多重免疫组织化学检查活检标本以评估其免疫细胞谱。分析临床结局。根据内镜特征比较免疫细胞谱，并与IBD患者的免疫细胞谱进行对比。
17例ICI诱导的结肠炎患者纳入研究。所有患者治疗后临床症状均有改善，11例患者（64.7%）接受了类固醇治疗。根据内镜特征，患者被分类为克罗恩病（CD）样（n = 3，17.6%）、溃疡性结肠炎（UC）样（n = 9，52.9%）或显微镜下结肠炎（MC）样（n = 5，29.4%）。在ICI诱导的结肠炎中，细胞毒性T细胞（Tc细胞）比辅助性T细胞（Th细胞）更占优势（P = 0.053），这种趋势在MC样亚型中最为明显（P = 0.020）。比较隐窝中浸润的CD8 +细胞数量时，UC样和MC样亚型的浸润细胞均明显多于CD样亚型（分别为P = 0.008和P = 0.016）。与IBD相比，IBD表现为Th占优势的特征，而CD样ICI诱导的结肠炎的Th细胞密度低于CD（P = 0.032），UC样ICI诱导的结肠炎的Tc密度高于UC（P = 0.045）。
对ICI诱导的结肠炎的T细胞亚群分析显示以Tc占优势的特征，这与IBD患者中观察到的Th占优势形成对比。Tc占优势的特征在UC样和MC样亚型中明显，CD8 +细胞有明显的隐窝浸润。Tc可能在ICI诱导的结肠炎的病理生理学中起重要作用。
