ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1612287
Bimodal Onset and Pan-Cancer Uniformity of Immune-Mediated Liver Injury: A Retrospective Cohort Study
Provisionally accepted
- 1Department of Respiratory and Critical Care Medicine, The First People's Hospital of Linhai, Taizhou, China
- 2Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
- 3Department of Respiratory and Critical Care Medicine, Taizhou First People's Hospital, Taizhou, China
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Background: Immune-mediated liver injury (IMLI) is a critical adverse event in patients treated with PD-1/PD-L1 inhibitors. The study aims to characterize the clinical heterogeneity, temporal dynamics, and immunological drivers of PD-1/PD-L1 inhibitor-associated IMLI and optimize surveillance and management strategies. Methods: We retrospectively recruited 373 IMLI patients. We evaluated clinical data, including liver injury patterns, severity, temporal trends, and immune cell subsets. Statistical analyses identified risk factors for severe IMLI and temporal dynamics. Results: Among 373 patients (median age: 65 years; male: 74.8%), IMLI severity was graded as G1 (53.9%), G2 (25.2%), G3 (17.9%), and G4 (2.7%), with hepatocellular (17.2%), mixed (42.6%), and cholestatic (40.2%) patterns observed. The median time to onset was 106-115 days across severity groups. In contrast, recovery time was significantly prolonged (G1/2: 14 days vs. G3/4: 23 days, P<0.05), and recovery-phase CD8⁺ T cells (524.9 vs. 270.68 cells/μL, P=0.026) were higher in severe cases. Bimodal onset peaks occurred at 1-2 months and 3-4 months, with 88% recovering within 100 days. No tumor-type differences existed in patterns (P=0.427) or severity (P=0.054). Elevated baseline NK cells (OR=1.004, P=0.036) predicted severe IMLI.Conclusions: IMLI demonstrates bimodal onset and pan-cancer uniformity, driven by systemic immune dysregulation. Baseline NK cells are potential predictors of severity. Risk-adapted monitoring within 4 months post-ICI and standardized protocols are recommended.
Keywords: immune-mediated liver injury, PD-1/PD-L1 inhibitor, clinical characteristic, Immune dysregulation, Management
Received: 15 Apr 2025; Accepted: 20 Jun 2025.
Copyright: © 2025 Song, Xu, Yu, Fu, Wang, Zhou, Hu and Xia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yang Xia, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang Province, China
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