Moreover, IFNγ stimulates JAK1-STAT1 signaling to induce SMAD7, which antagonizes TGFβ downstream SMAD3 phosphorylation, nuclear translocation, and activation of responsive genes (such as collagen genes).56 Therefore, we hypothesized that shifting the sarcoma microenvironment from a TGFβ-dominated one to an IFNγ-dominated one would overcome the collagen barrier that blocks T-cell infiltration. This evidence concerns the gene SMAD3 and sarcoma.