The rnaset2 oncosuppressor protein regulates both differentiation and polarization in human macrophages

T2 ribonucleases represent an evolutionarily conserved family of extracellular ribonucleases mainly involved in host defense and stress response. The human RNASET2 protein has been consistently associated with a marked tumor suppressive activity, which is likely carried out by establishing a cross- talk between cancer cells-derived RNASET2 and the tumor microenvironment (TME). Indeed, independent xenograft-based or syngeneic murine experimental models clearly showed that increased RNASET2 expression levels are consistently associated with a marked suppression of both tumorigenic and metastatic potential in vivo. Noteworthy, histological characterization of RNASET2- suppresed tumors revealed a marked inflammatory infiltration within the tumor mass, represented by murine stromal cells belonging to the M1 anti-tumorigenic subclass of macrophages. In this work, we established an in vitro experimental model to recapitulate the activity of human RNASET2 protein on cells belonging to the monocyte/macrophage lineage that we previously observed in vivo. We present here preliminary results from human promyelocytic THP-1 cells exposed to elevated RNASET2 protein levels in two independent experimental settings. Treatment of human THP-1 cells with either recombinant human RNASET2 protein of with conditioned media from RNASET2- overexpressing 22Rv1 prostate cancer cells confirmed the role of this protein in regulating the biology of human macrophages, although we observed a slightly different response in the two experimental settings. Taken together, these data provide a further confirmation of the ability of human RNASET2 to affect human macrophage’s differentiation and polarization pattern in vitro.