Overexpression of Murine in a Colon Syngeneic Mouse Carcinoma Model Leads to Rebalance of Intra-Tumor M1/M2 Macrophage Ratio, Activation of T Cells, Delayed Tumor Growth, and Rejection.

Human RNASET2 acts as a powerful oncosuppressor protein in in vivo xenograft-based murine models of human cancer. Secretion of RNASET2 in the tumor microenvironment seems involved in tumor suppression, following recruitment of M1-polarized macrophages. Here, we report a murine -based syngeneic in vivo assay. BALB/c mice were injected with parental, empty vector-transfected or murine -overexpressing mouse C51 or TS/A syngeneic cells and tumor growth pattern and immune cells distribution in tumor mass were investigated. Compared to control cells, mouse -expressing C51 cells showed strong delayed tumor growth. CD86 M1 macrophages were massively recruited in expressing C51-derived tumors, with concomitant inhibition of MDSCs and CD206 M2 macrophages recruitment. At later times, a relevant expansion of intra-tumor CD8 T cells was also observed. After re-challenge with C51 parental cells, most mice previously injected with -expressing C51 cells still rejected C51 tumor cells, suggesting a Rnaset2-mediated T cell adaptive immune memory response. These results point at T2 RNases as evolutionary conserved oncosuppressors endowed with the ability to inhibit cancer growth in vivo through rebalance of intra-tumor M1/M2 macrophage ratio and concomitant recruitment of adaptive anti-tumor CD8 T cells.