However, while Exo interact with many T-cell subtypes, their major effect is on the inhibitory population that over-produces IL-10 and TGF-β1, increases the expression of negative immune checkpoints such as CTLA-4 and hyper-phosphorylates SMAD2/3, which has been implicated in the transcription of intracellular inhibitory signals that restrain the anti-melanoma immune response [62]. Here, TGFB1 is linked to melanoma.