Immune checkpoint inhibitor-related endocrinopathies: from immune crosstalk to predictive biomarkers and precision management.
Immune checkpoint inhibitors (ICIs) have significantly prolonged patient survival in cancer therapy; however, overactivated immune responses can lead to endocrine immune-related adverse events (irAEs), primarily manifesting as thyroid dysfunction, hypophysitis, adrenal insufficiency, and insulin-dependent diabetes mellitus. Some of these endocrine injuries are irreversible and lack early warning indicators. This narrative review summarizes current evidence regarding the mechanisms underlying ICI-induced endocrine toxicities, including immune checkpoint pathways, organ-specific autoimmune responses, host-related factors, predictive biomarkers, and emerging precision management strategies. It summarizes potential predictive biomarkers, including thyroid autoantibodies, cytokine profiles, and single-cell sequencing, and discusses emerging approaches, including imaging-based assessment, liquid biopsy, and multidimensional prediction models, while emphasizing their current limitations and the need for prospective validation. Finally, by integrating organ-specific mechanistic evidence, biomarker-based prediction, and risk-stratified monitoring, this review frames these advances within the concept of "proactive endocrine protection," emphasizing the transition from passive toxicity management toward earlier identification and individualized surveillance.
Authors
Liu Liu, Xu Xu, Chen Chen, Zhang Zhang, Wang Wang, Yan Yan, Xie Xie, Li Li, Cai Cai
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