In tumor cells, inhibition of AKT activation impairs SMAD3 phosphorylation and in turn abrogates SMAD3-mediated collagen induction, suggesting that crosstalk between AKT signaling and SMAD3 phosphorylation upregulates collagen.17 To remove collagen’s obstruction of T-cell infiltration, current collagen-inhibition methods focus on targeting TGFβ1-induced collagen expression, but targeting TGFβ alone via systemic administration of a monoclonal antibody only slightly enhanced T-cell infiltration in humanized tumor models18 owing to the constitutively high expression of TGFβ in tumor cells. This evidence concerns the gene SMAD3 and neoplasm.