SMAD3 and neoplasm: And consistent with those results, we found that IL-37b markedly promoted the secretion of TGF-β and while dramatically inhibiting the secretion of IL-6, IL-8, IL-1β, TNF-α and MMP2, suggesting that IL-37b establishes a positive feedback loop to regulate TGF-β/Smad3 signaling by promoting the secretion of tumor-suppressive cytokines and inhibiting the secretion of the oncogenic cytokines to achieve HCC tumor-suppression (Figure 6D).