AB009. Review of case characteristics and exploration of mechanisms of thymoma shrinkage after glucocorticoid therapy

Background: Thymomas are frequently associated with autoimmune diseases. For such patients, stabilizing the autoimmune condition prior to surgery is essential to avoid complications. Glucocorticoids (GCs) are the first-line therapy for autoimmune diseases, and clinical observations suggest that GC treatment may reduce thymoma size, facilitating surgical resection. This study aims to investigate the mechanism underlying GC-induced thymoma shrinkage through case analysis and in vitro experiments.

Methods: We retrospectively analyzed 12 patients with thymic disease and autoimmune disorders treated at our center between January 2020 and December 2024. Data were collected on tumor volume reduction following GC therapy, including mean reduction rate and duration of hormone use. Comparisons were made with thymoma patients without GC treatment (including those with concurrent myasthenia gravis and pure thymoma cases). Recombinant glucocorticoid receptor alpha (GRα) expression levels were measured in thymoma tissues from GC-treated patients, and the relationship between GRα and the Nuclear Factor kappa-light-chain-enhancer of activated B cells/B-cell lymphoma-2 (NF-κB/Bcl-2) pathway was analyzed in thymoma cells.

Results: The mean duration of GC therapy in this cohort was 2.2 months, with an average reduction of 53.29% in the maximum cross-sectional area of the thymoma. This significant shrinkage did not increase surgical complications. Furthermore, no tumor recurrence was observed during follow-up, and all patients achieved stable control of their autoimmune disease. Pathological examination confirmed that these cases were predominantly type B2 and/or B3 thymomas. Compared to untreated patients (including those with concurrent myasthenia gravis and pure thymoma cases), GC-treated patients exhibited higher GRα expression in thymoma tissues. In vitro experiments demonstrated that the NF-κB/Bcl-2 pathway is present in thymoma cells and regulated by GCs. GC treatment upregulated glucocorticoid receptor (GR) expression while increased GRα levels suppressed downstream NF-κB and Bcl-2 expression.

Conclusions: These findings highlight the beneficial role of preoperative GC therapy in thymoma patients with autoimmune diseases. GCs modulate the thymoma microenvironment and induce apoptosis via the GRα–NF-κB/Bcl-2 pathway, offering a novel clinical strategy for managing these patients.

Keywords: Thymoma; autoimmune disease; glucocorticoids (GCs); glucocorticoid receptor (GR)