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. Here, INHBE is linked to neoplasm.