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

Abstract Background Papillary thyroid cancer (PTC) is frequently associated with inflammation and lymph node (LN) metastasis. Single-cell RNA sequencing (scRNA-seq) can uncover rare sub-populations of cells and explore functional heterogeneity of tissue microenvironments. Here, through scRNA-seq analysis of a metastatic PTC (PTC-M) and its adjacent normal tissues as well as a PTC tumor without metastasis, we identified the heterogeneity of macrophages, dendritic cells (DCs), and T cells in the PTC-M sample, implying the role of the immunosuppressive components in the development and metastasis of PTC. Results Our results demonstrated that alternatively activated (M2) macrophages, conventional-type 2 dendritic cells (cDC2s), and regulatory T cells (Tregs) were associated with greater lymph node metastases and more advanced stages, whereas monocytes and B cells could play an anti-tumor role. Notably, a cluster of tumor-associated LAMP3 + CCL22 + DC2 cells expressed diverse immune-related ligands and exhibited the potential to recruit CD4 + T cells by cell-cell communications in the microenvironment. Conclusion In the present study, we provided insights into the immune landscape at a single-cell level and expanded potential therapeutic strategies for PTC with metastasis. The results supported the theory that certain clusters of myeloid cells and Tregs participated in modulating the tumor-associated environment and facilitating tumor progression or metastasis.