In addition, the employment of activin receptor‐like kinase5 (ALK‐5) inhibitor EW‐7197 induced ubiquitin‐mediated degradation of Smad4 and subsequently up‐regulation of eomesodermin in CD8+ T cells of melanoma‐bearing mice, thus enhancing the cytotoxic effect of T cells and leading to the regression of melanoma growth. Here, SMAD4 is linked to melanoma.