Pre-existing Thyroiditis Ameliorates Papillary Thyroid Cancer: Insights From a New Mouse Model

Papillary thyroid cancer (PTC) often co-occurs with Hashimoto's thyroiditis, an association that has long been reported in clinical studies yet remains controversial. Some studies, in fact, have suggested a protective effect of thyroiditis while others have not. We generated a mouse model where PTC and thyroiditis develop in a predictable manner, combining the oncogenic drive of the BRAF(v600E) mutation (inducible by tamoxifen) to the thyroiditis susceptibility of the NOD.H2(h4) strain (inducible by iodine). A total of 113 NOD.H2(h4)_TPO-CRE-ER_BRAF(V600E) mice (50 followed throughout lifetime and 63 sacrificed at 16 weeks post tamoxifen) were used to determine whether the PTC phenotype differs when thyroiditis precedes or coincides with the onset of PTC. Mice with pre-existing thyroiditis lived longer (median survival of 28.2 weeks post tamoxifen) than those with concomitant (25.6 weeks) or no (24.5 weeks) thyroiditis (P < 0.01 by Laplace regression). PTC developed less frequently (33%) in the pre-existing thyroiditis group than the concomitant (100%) or no (100%) thyroiditis groups (P < 0.001 by chi-squared) and showed less aggressive histopathological features. The intratumoral mononuclear cell infiltration was more prominent in mice with pre-existing thyroiditis (P = 0.002 vs the other groups) and sustained by a significant expansion of effector memory CD8 + T cells and CD19 + B cells. These findings shed light on the controversial PTC-thyroiditis association and emphasize the contribution of intratumoral T and B lymphocytes to the evolution of PTC.

Automated summary

In a mouse model study, it was found that papillary thyroid cancer (PTC) developed more frequently and displayed more aggressive pathological features when occurring concurrently with Hashimoto's thyroiditis. Mice with pre-existing thyroiditis had longer survival time, lower incidence of PTC, and more prominent intratumoral mononuclear cell infiltration. These findings highlight the contribution of intratumoral T and B lymphocytes to the evolution of PTC.