Thymic epithelial tumors at the crossroads of immunity, autoimmunity, and immunotherapy - PubMed
6 hours ago
- #Autoimmunity
- #Immune checkpoint inhibitors
- #Thymic epithelial tumors
- Thymic epithelial tumors (TETs) are located at the intersection of cancer, central tolerance, and autoimmunity.
- TETs arise in the thymus, an immune-rich organ responsible for T-cell education.
- Despite low tumor mutational burden (TMB) and microsatellite stability, TETs show paradoxical behavior under immune checkpoint inhibition.
- Disruption of AIRE/FEZF2-driven antigen expression and impaired regulatory T-cell generation lead to autoreactive T-cell escape and paraneoplastic syndromes.
- TET patients treated with immune checkpoint inhibitors (ICIs) experience high frequency and severity of immune-related adverse events, despite modest response rates.
- Emerging biomarkers like autoantibody profiles and T- and B-cell perturbations may help stratify risk and guide treatment.
- Rational therapeutic strategies include VEGF-TKI-ICI combinations, radiotherapy-ICI approaches, and perioperative immunotherapy.
- TETs serve as a model to understand central tolerance failure, impacting tumor immune response and patient toxicity risks.