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.H2h4_TPO-CRE-ER_BRAFV600E 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 intra-tumoral mononuclear cell infiltration was more prominent in mice with pre-existing thyroiditis (p= 0.002 versus 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 intra-tumoral T and B lymphocytes to the evolution of PTC.
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