These data provide evidence that activin (i) signals non-canonically through the PI3K/AKT pathway and is associated with reduced survival time in a mouse model of CRC, (ii) is necessary for TGF-β associated improved outcomes in CRC (iii) on a local level, is associated with increased markers of T-cell exhaustion in both the tumoral and stromal compartments of the TME, and drives tumor growth in vivo and migration in vitro. This evidence concerns the gene INHBE and colorectal carcinoma.