Transcriptomic signatures associated with autoimmune thyroiditis in papillary thyroid carcinoma and cancer...

Area of Science:

• Immunology
• Oncology
• Endocrinology

Background:

• Immune checkpoint inhibitors (anti-PD-1/PD-L1) can cause thyroid dysfunction in up to 20% of patients.
• The underlying mechanisms linking immunotherapy-induced thyroid dysfunction and autoimmune thyroiditis, such as Hashimoto thyroiditis (HT), remain unclear.

Purpose of the Study:

• To investigate shared molecular signatures between papillary thyroid carcinoma (PTC) with HT and immunotherapy-induced thyroid immune-related adverse events (irAEs).
• To identify potential therapeutic targets for managing thyroid irAEs during cancer immunotherapy.

Main Methods:

• Clinical characteristics analysis of 468 PTC patients from two cohorts and meta-analysis of 22,155 PTC patients.
• Transcriptome and single-cell transcriptome analysis of PTC patient cohorts.
• Correlation analysis of 3,318 thyroid adverse events across 24 tumor types.

Main Results:

• Hashimoto thyroiditis (HT) was negatively associated with recurrence in papillary thyroid carcinoma (PTC) patients.
• PTC patients with HT showed enrichment of macrophages and CD8+/CD4+ cytotoxic T cells, with CD8+ T cells correlating with disease-free survival.
• Shared molecular signatures, including PD-1-related genes and CD8+ T cell activity, were identified between HT and thyroid irAEs.

Conclusions:

• Shared molecular signatures exist between Hashimoto thyroiditis and immunotherapy-induced thyroid immune-related adverse events.
• CD8+ T cells and CD3D may play crucial roles in thyroid immune-related adverse events, offering potential targets for managing adverse events in cancer immunotherapy.