Hashimoto's thyroiditis both promotes and protects against papillary thyroid cancer

The growing body of evidence suggests a complicated association between papillary thyroid cancer (PTC) and Hashimoto's thyroiditis (HT). Although HT is a major risk factor for PTC development, it is also associated with improved patient outcomes. However, the molecular mechanisms between these two diseases remain unclear. This narrative review summarizes clinical evidence that connects HT with PTC and examines how these two conditions interact. It explores the involvement of CD4⁺ T-cell subsets, regulatory T cells, CD8⁺ T cells, tumor-associated macrophages, and key immunological molecules in remodeling the tumor immune microenvironment (TIME) during HT. We also discuss the contributions of genetic predisposition, environmental factors, thyroid-stimulating hormone and autoantibodies, non-coding RNA regulatory networks, and the gut microbiota to the relationship between the two diseases. Further research is needed to fill the gaps in our understanding of HT and PTC linkages, aiming to provide a theoretical foundation for developing personalized therapies that target the TIME.