Taken together, these results support the role of T2 Ribonucleases as evolutionary conserved tumor suppressor genes endowed with the ability to inhibit cancer growth in vivo also in immunocompetent experimental models, through rebalance of intra-tumor M1/M2 macrophage polarization towards TNFα-producing M1-type macrophages and recruitment of adaptive CD8+ T cells. Here, TNF is linked to neoplasm.