Figure 1.
Role of the PD-1/PD-L1 pathway in thyroid pathogenesis. Upper panel graphical displays the thyroid immune microenvironment in AITD (Graves' disease and Hashimoto's thyroiditis, A), thyroid immune-related adverse events (B), and thyroid cancer (C). Lower panel. At the molecular level, the highly activated lymphocytes, which are characterized by the expression of PD-1 and IFNγ, are in close contact with thyrocytes and thyroid tumor cells. Either IFNγ or/and BRAFV600E induce the expression of PD-L1 by the epithelial cells, which binds to its receptor PD-1 on lymphocytes and thereby restrains autoimmune attacks in AITD (D) and promotes thyroid tumor immune tolerance (F). Note that both AITD and TC release the serum-soluble form of PD-L1, which may contribute with the tissue PD-L1 to the immune escape and be considered as biomarkers and therapeutic targets (sPD-L1, E). Abbreviations: AITD, Autoimmune thyroid disease; Anti-TSH-R-ab, Anti-receptor of the thyroid-stimulating hormone antibody; Anti-TPO-ab, Anti-thyroid peroxidase antibody; Auto‑ab, Auto-antibodies; CLT, Chronic lymphocytic thyroiditis; GD, Grave's disease; IFNγ, Interferon-gamma; irAEs, Immune-related adverse events; PD-1, Programmed-cell death receptor 1; PD-L1, Programmed-cell death ligand 1; SNP, Single nucleotide polymorphism.