Since their approval in 2011, immune checkpoint inhibitors (ICIs) have become a cornerstone of cancer treatment, significantly improving overall survival rates [1]. ICIs work by targeting regulatory immune checkpoint molecules, thereby activating the immune system to elicit antitumor immune responses. To date, three classes of ICIs have been approved for clinical use. The first approved agent targeting cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) is ipilimumab, which is indicated for the treatment of metastatic melanoma and renal cell carcinoma [2]. The second class includes antibodies targeting programmed cell death protein 1 (PD-1), such as pembrolizumab and nivolumab, which are used for advanced-stage melanomas and a range of cancers including non-small cell lung cancer (NSCLC), renal cell carcinoma, and head and neck cancers. The third class targets programmed death ligand 1 (PD-L1) and includes antibodies such as atezolizumab, avelumab, and durvalumab, which are approved for the treatment of cancers such as urothelial carcinoma, NSCLC, hepatocellular carcinoma, and Merkel cell carcinoma [2]. Although ICIs have transformed cancer therapy, they can cause adverse effects due to immune system overstimulation. These side effects, collectively known as immune-related adverse events (irAEs), may manifest as skin rash, colitis, pneumonitis, myositis, vasculitis, pericarditis, or arthritis. irAEs most commonly occur 4 to 12 weeks after initiating treatment but can also arise immediately after administration, months later, or even following treatment discontinuation [3]. The colon is one of the most commonly affected sites of ICI-induced irAEs, with an incidence ranging from 15% to 30% of all cases [4,5]. According to the American Society of Clinical Oncology, diarrhea is defined as the occurrence of three or more bowel movements per day, while colitis is characterized by symptoms such as abdominal pain, bloody diarrhea, fever, and mucorrhea [6]. When ICI-induced colitis is suspected, laboratory and stool tests should be performed to exclude other potential causes, such as infections. Colonoscopy with biopsy is the gold standard for diagnosis, with typical endoscopic findings including loss of vascularity, erythema, edema, a granular appearance, friability, erosions, and ulcers [5,6]. Histological examination often reveals acute and chronic inflammation, such as cryptitis, crypt abscesses, epithelial apoptosis, and occasionally crypt distortion or microscopic colitis. Although the precise mechanism underlying ICI-induced colitis remains unclear, it is thought to involve effector T-cell hyperactivation, an increase in memory T cells, cytokine activation, and interactions between the gut microbiome and the immune system [6]. Identified risk factors include the gut microbiome, use of nonsteroidal anti-inflammatory drugs, higher doses of ipilimumab, pre-existing autoimmune disorders such as inflammatory bowel disease or rheumatic disease, and elevated serum IL-17 levels [6]. Because the CTLA-4 pathway relies on antigen-presenting cells and functions upstream of the PD-1 and PD-L1 signaling pathway, ICI-induced colitis occurs more frequently with ipilimumab. A recent systematic review and meta-analysis revealed that the incidence rates of ipilimumab-induced diarrhea and colitis are 33% and 7%, respectively, compared with 10% and 2% for anti-PD-1/PD-L1 therapies [7]. However, the combination of ipilimumab and nivolumab is associated with relatively higher incidence rates of diarrhea and colitis, ranging from 21% to 37% and from 4% to 8%, respectively [7]. There have been no epidemiological reports on the incidence of ICI-induced colitis in Korea. In this context, Kim et al. [8] provided valuable insights into the incidence and risk factors of ICI-induced colitis in Korean patients with cancer. Data were collected retrospectively from two tertiary referral centers in Korea, and the authors categorized both ICI-induced diarrhea and colitis under the term ICI-induced colitis. The overall incidence rate of ICI-induced colitis was 3.52% (52/1,478). This rate, which may vary depending on the type and dose of ICI agents and patient characteristics such as cancer type, tended to be somewhat lower than those reported in Western populations. Most patients were treated with anti-PD-1/PD-L1 agents, and the incidence of colitis was 3.5% (18/516) for pembrolizumab, 5.5% (22/401) for nivolumab, and 1.6% (8/495) for atezolizumab. Notably, among the seven patients treated with ipilimumab, no cases of colitis were observed; this is inconsistent with findings from previous studies [7]. However, colitis was reported in 30.8% (4/13) of patients treated with the combination of nivolumab and ipilimumab, aligning with incidence rates reported in other studies [7]. Therefore, the incidence of colitis associated with ipilimumab could change if additional data were collected. In a multivariate regression analysis of risk factors for ICI-induced colitis, the combination of nivolumab and ipilimumab was the only statistically significant factor (odds ratio = 9.768, p = 0.006). However, no patients with autoimmune diseases were included in the study, suggesting that additional risk factors might be identified with larger datasets. These findings highlight the need for monitoring and prevention strategies for colitis, particularly in patients receiving combination therapy with ipilimumab and nivolumab. Nevertheless, most patients with ICI-induced colitis in this study experienced mild symptoms and responded well to supportive care without requiring discontinuation of ICI therapy.

This study represents the first step in epidemiologic analyses of ICI-induced colitis in Korean patients. However, as a retrospective study, it is challenging to establish a causal relationship with ICI therapy, and there are limitations in adequately evaluating other possible causes, such as infections, particularly in patients with mild colitis symptoms. In addition, the small number of cases for certain ICI agents and cancer types limits the study’s generalizability. Further studies on the influence of the microbiome, serologic markers, medical history, and medications could provide valuable information for identifying Korean patients at risk for ICI-induced colitis and clarifying the mechanisms underlying irAEs.