Single‑cell transcriptomic analysis revealed the tumor‑associated microenvironment of papillary thyroid carcinoma with metastasis.

Abstract

Papillary thyroid cancer (PTC) is frequently associated with inflammation and lymph node metastasis. Single-cell RNA sequencing (scRNA-seq) is a powerful tool to uncover rare cellular subpopulations and investigate the diverse functions inside tissue microenvironments. In the present study, scRNA-seq analysis was employed to analyze the differences in macrophages, dendritic cells (DCs) and T cells between a metastatic PTC (PTC-M) and its adjacent normal tissues, as well as a PTC tumor without metastasis. The findings revealed significant heterogeneity in immune cell populations in PTC-M, suggesting that immunosuppressive components contribute to the development and metastasis of PTC. The current study revealed that the presence of alternatively activated M2 macrophages, conventional type 2 DCs (DC2s) and regulatory T cells (Tregs) was associated with increased lymph node metastasis and a more advanced stage of cancer. On the other hand, monocytes and B cells may have a beneficial effect in fighting against tumors. A group of tumor-associated DC2s expressing both LAMP3 and CCL22 were shown to have a variety of immune-related ligands. These cells have the ability to attract CD4+ T cells through communication between cells in the microenvironment. In this study, the immunological composition was examined at the level of individual cells and new prospective treatment approaches for PTC-M were identified. The results support the hypothesis that myeloid cells and Tregs significantly contribute to tumor progression and metastasis by shaping the tumor microenvironment.