Although high TGF-β-signaling in tumors leads to immune tolerance, loss of epithelial or fibroblast TGF-β signaling increases inflammation and promotes tumorigenesis: Epithelial loss of Smad4 increases inflammatory infiltration and development of dextran-sulfate-induced colon tumors; and loss of fibroblast TGF-βRII has been associated with increased inflammation, DNA damage in epithelial cells, and tumor formation in the forestomach (Achyut et al., 2013; Means et al., 2018). This evidence concerns the gene TGFB1 and colonic neoplasm.