Due to these effects on the immune system and the association between TGF-beta and resistance to ICIs, combining TGF-β inhibitors with ICIs emerged as a feasible strategy to activate immune machinery.115 In a recent phase II open-label trial, the combination of vactosertib (selective TGF-β receptor I kinase inhibitor) and pembrolizumab led to an ORR of 15.2% in patients with MSS CRC who had progression under all available options. This evidence concerns the gene TGFB1 and colorectal carcinoma.