Hashimoto's thyroiditis influences tumor cell states and intratumoral microbiota in papillary thyroid carcinoma.

Hashimoto's thyroiditis is associated with reduced lymph node metastasis in papillary thyroid carcinoma, suggesting that the autoimmune microenvironment may influence tumor progression. We utilized single-cell RNA sequencing and intratumoral 16S ribosomal RNA gene sequencing to investigate malignant epithelial cell states and microbial features in PTC with and without Hashimoto's thyroiditis. Tumors with Hashimoto's thyroiditis exhibited malignant epithelial populations enriched for innate immune signaling programs and showed increased intratumoral microbial diversity with reduced abundance of several Gram-negative bacteria, particularly Pseudomonas. Within the Hashimoto's thyroiditis subgroup, lymph node metastasis was associated with increased Gram-negative bacterial abundance. Functional experiments further showed that Pseudomonas-derived lipopolysaccharide enhanced thyroid cancer cell migration in vitro and in vivo. These findings suggest that Hashimoto's thyroiditis reshapes both epithelial transcriptional states and the intratumoral microbial environment, potentially contributing to a less aggressive tumor phenotype.