{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:53:29Z","timestamp":1792511609002,"version":"4.5.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"Background<\/jats:title>With the widespread use of immune checkpoint inhibitors (ICIs), the management of immune-related adverse events (irAEs) has become increasingly important. ICI-induced pancreatic injury (ICI-PI) is rare, and its clinical characteristics remain unclear. This study aimed to clarify the risk factors for the development of ICI-PI and prognostic impact of ICI-PI.<\/jats:p><\/jats:sec>Methods<\/jats:title>A total of 1039 patients with malignant tumors who received ICI therapy were recruited from September 2014 to December 2024 for this retrospective study. The clinical and pathological characteristics of ICI-PI, including risk factors and prognostic impact, were analyzed. The onset of ICI-PI and irAEs of other organs were defined according to CTCAE ver5.0. The pathological characteristics were evaluated using pancreatic tissue specimens obtained by endoscopic ultrasound-guided fine-needle biopsy.<\/jats:p><\/jats:sec>Results<\/jats:title>Of the 982 patients (703 males, 279 females; median age, 71.1 years) included in the study, 48 (4.9%) developed ICI-PI (Grades 2, 3, and 4 in 41, 3, and 4 cases, respectively), and 6 patients (0.6%) developed pancreatitis. Multivariate analysis revealed that the high serum amylase levels before ICI administration (odds ratio, 6.10; 95%CI, 2.55-14.6; P<\/jats:italic> &lt; 0.001) and the onset of irAE in other organs (odds ratio, 3.49; 95%CI, 1.88-6.49; P<\/jats:italic> &lt; 0.001) were independent risk factors for ICI-PI development. The incidence of other organ irAEs was significantly higher in the ICI-PI onset group than in the ICI-PI non-onset group (P<\/jats:italic> &lt; 0.001). Additionally, there was significantly better overall survival in the ICI-PI onset group than in the ICI-PI non-onset group (P<\/jats:italic> &lt; 0.001), which was corroborated by a landmark analysis. Also, pathological examination of ICI-related pancreatitis using multiplex fluorescence immunohistochemistry demonstrated infiltration of predominantly CD8 positive T lymphocytes contained abundant granzyme B into the pancreatic parenchyma.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>High serum amylase levels before ICI administration and development of other organ irAEs were identified as novel risk factors for ICI-PI onset, and the long-term prognosis was better in patients with ICI-PI. This finding suggests that thorough systemic management, including proactive evaluation of serum amylase levels and comprehensive monitoring for various irAEs, can contribute to early detection of ICI-PI, potentially leading to improved patient outcomes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1590992","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T05:21:46Z","timestamp":1753766506000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Risk factors and long-term prognostic impact of immune related pancreatic injury in patients receiving immune checkpoint 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