Transcriptome Analysis Revealed Potential Neuro-Immune Interaction in Papillary Thyroid Carcinoma Tissues

Background: A recent study reported that papillary thyroid carcinoma (PTC) was associated with increased adrenergic nerve density. Meanwhile, emerging evidence suggested that tumor-innervating nerves might play a role in shaping the tumor microenvironment. We aimed to explore the potential interaction between neuronal markers and tumor microenvironmental signatures through a transcriptomic approach. Methods: mRNA sequencing was conducted using five pairs of PTC and adjacent normal tissues. The Gene Set Variation Analysis (GSVA) was performed to calculate enrichment scores of gene sets related to tumor-infiltrating immune cells and the tumor microenvironment. The potential interaction was tested using the expression levels of a series of neuronal markers and gene set enrichment scores. Results: PTC tissues were associated with increased enrichment scores of CD8 T cells, cancer-associated fibroblasts, mast cells, and checkpoint molecules. The neuronal marker for cholinergic neurons was positively correlated with CD8 T cell activation, while markers for serotonergic and dopaminergic neurons showed an inverse correlation. Conclusion: Distinct neuronal markers exerted different correlations with tumor microenvironmental signatures. Tumor-innervating nerves might play a role in the formation of the PTC microenvironment.