Immune checkpoint inhibitors in thymic epithelial tumors: current evidence, immune-related toxicity, and...

Thymic epithelial tumors (TETs) are rare mediastinal malignancies with unique immunobiological features related to thymic immune tolerance. Although immune checkpoint inhibitors (ICIs) have shown clinical activity, especially in thymic carcinoma, their use is limited by frequent and sometimes severe immune-related adverse events (irAEs), particularly in thymoma. This review summarizes current evidence on the efficacy, toxicity, biomarkers, and perioperative implications of ICIs in TETs.

A narrative review was conducted using PubMed, Web of Science, and Embase for English-language studies on ICIs in TETs published from database inception to September 2025. Reference lists of relevant articles and guideline papers were also manually screened. Prospective trials, retrospective cohorts, guideline papers, and key mechanistic studies were prioritized, with emphasis on histology-specific efficacy, irAEs, biomarkers, and perioperative application.

Current evidence suggests that ICIs have more consistent antitumor activity in thymic carcinoma than in thymoma. In contrast, thymoma carries a substantially higher risk of severe early irAEs, particularly myocarditis, myositis, and myasthenia gravis overlap syndromes. Biomarkers such as programmed death-ligand 1 (PD-L1) expression and immune-related signatures remain promising but are not yet sufficiently validated for routine patient selection. Perioperative immunotherapy is an emerging strategy, but current evidence remains limited and safety concerns are significant.

ICIs represent a promising treatment option for selected patients with advanced TETs, particularly thymic carcinoma, but their clinical use remains restricted by toxicity and limited evidence. Future progress will depend on better risk stratification, biomarker-guided selection, and safer multidisciplinary integration.