Integrative single-cell transcriptome analysis reveals immune suppressive landscape in the anaplastic thyroid cancer

The tumor immune microenvironment (TIME) in ATC is a complex and diverse ecosystem. It is essential to have a comprehensive understanding to improve cancer treatment and prognosis. However, TIME of ATC and the dynamic changes with PTC has not been revealed at the single-cell level. Here, we performed an integrative single-cell analysis of PTC and ATC primary tumor samples. We found that immunosuppressive cells and molecules dominated the TIME in ATC. Specifically, the level of infiltration of exhausted CD8+ T cells, and M2 macrophages was increased, and that of NK cells, B cells, and M1 macrophages was decreased. The cytotoxicity of CD8+ T cells, γδT cells, and NK cells was decreased, and immune checkpoint molecules, such as LAG3, PD1, HAVCR2, and TIGIT were highly expressed in ATC. Our findings contribute to the comprehension of TIME in both PTC and ATC, offering insights into the immunosuppressive factors specifically associated with ATC. Targeting these immunosuppressive factors may activate the anti-tumor immune response in ATC.