CircMERTK modulates the suppressive capacity of tumor-associated macrophage via targeting IL-10 in colorectal cancer

Macrophages represent the major population in the tumor microenvironment (TME). Recent studies have demonstrated circular RNAs (circRNAs) are implicated in the development and progression of different immune responses and immune diseases. However, the role of circRNAs in the development of tumor-associated macrophages (TAM) remains unknown. Here, we used the circRNA sequencing to identify the differentially expressed circRNAs (DEcircRNAs) in TAM-like cell induced by culture medium of colorectal cancer cell lines. Of note, the expression of circMERTK was remarkably overexpressed in TAMs. The ISH assay displayed that the expressions of circMERTK were mainly overlapped with macrophages marker CD68, and the abundance of circMERTK in CRC tissues was much higher than that in matched normal tissues. Functionally, circMERTK knockdown resulted in attenuated CD8+ T cell apoptosis in the co-culture assay, indicating that circMERTK could have an impact on the immunosuppressive activity of TAM-like cell. Mechanically, TAM-like cell could exert immunosuppressive activity via circMERTK/miR-125a-3p/IL-10 axis. These data suggested that circMERTK could play an important role in TAM activation, and may serve as a potential therapeutic target for CRC.