Concerning Tregs, one of the major suppressors of anti-tumour immune surveillance (Flavell et al, 2010), Smad4-independent development of Tregs in our model and Smad2/3-independent development of nTregs in vivo (Gu et al, 2012) indicate that Treg development is Smad-independent. The gene discussed is SMAD2; the disease is neoplasm.