Cytoplasmic IL-37 translocates to the nucleus and reduces inflammatory response via Smad3.16,39 TGF-β/Smad3 also can regulate CTL functions during tumor immune escape.40 We observed that TGF-β inhibited the secretion of IFN-γ to a similar extent in splenic CD8+ T cells isolated of IL-37tg and WT mice activated by αCD3/αCD28-conjugated beads (Fig. 7j), demonstrating that IL-37 participating in CD8+ T cell dysfunction does not seem to depend on TGF-β/Smad3 signaling pathway. This evidence concerns the gene SMAD3 and neoplasm.