Regulation of macrophage differentiation and polarization pattern by human RNASET2 protein

ABSTRACT The human RNASET2 gene encodes for an evolutionarily conserved, extracellular ribonuclease, whose secretion by cancer cells in the tumor microenvironment (TME) is likely involved in tumor suppression. Material and method Indeed, in two independent in vivo xenograft-based experimental models, high human RNASET2 expression levels were 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, thus suggesting the occurrence of a RNASET2-mediated non cell-autonomous oncosuppressive role. Results and discussion We thus speculate that early-stage tumor cells actively secrete RNASET2 in order to provide an “alarmin-like” danger signal for cells belonging to the monocyte/macrophage lineage, whose role would be to trigger an effective oncosuppressive host immune response. In order to further validate in vitro the role of RNASET2 in macrophage differentiation and polarization previously observed in vivo, we present here preliminary results from human promyelocytic THP-1 cells treated with either human recombinant RNASET2 protein or conditioned media from RNASET2-overexpressing 22RV1 prostate cancer cells. Conclusion Taken together, these data provide a further confirmation of the ability of human RNASET2 to affect human macrophage’s differentiation and polarization pattern in in vitro experimental settings.