The presence of tertiary lymphoid structures (TLSs) associates with improved anti-tumor immunity, and as such, understanding why some tumors develop TLSs is of prime interest. In the current issue of Cancer Cell, Kirschstein et al. demonstrate that TGFβ-driven programming of myofibroblastic cancer-associated fibroblasts blocks reticular fibroblast differentiation and TLS formation in pancreatic cancer, a barrier reversible by TGFβR1 inhibition.