Immune response against Wilms Tumor: characterization of cellular and molecular interactions and identification of novel therapeutic targets

Wilms tumor (WT) is a pediatric kidney tumor that accounts for 6-7% of children’s malignant tumors. WT cells arise from embryonic mesenchymal renal progenitors, not differentiated, remaining in the organ after birth. The classic triphasic WT contains a mixture of undifferentiated blastemal, differentiated epithelial cells, and stromal elements, whereas individual cell types may predominate in some tumors. Moreover, as human mesenchymal stem cells (MSCs), these cells have the ability to differentiate in many tissue lineages. In particular, stromal-like WT (str-WT) display morphological, phenotypic, and biological features comparable to MSCs, suggesting they could play a significant role in the interactions with immune cells in the tumor microenvironment. The role of immune cells in the response against WT is still unclear, because of the very few data available; it is of note, however, that the presence of leukocyte infiltrate and a pro-inflammatory milieu have been described. In view of the similarity between MSCs and stromal-like WT cells, the aim of this study is to investigate the immunoregulatory properties of WT cells towards Natural Killer (NK) cells and the immunoregulatory mechanisms taking place in the tumor microenvironment. Our data showed the molecular interactions between str-WT cells and NK lymphocytes, resulting in different outcomes presumably occurring in the WT microenvironment.