Nature 554, 538–543 & 544–548 (2018)

Increased expression of the morphogen TGF-β is associated with poor prognosis in many cancers. In Nature, Tauriello et al. and Mariathasan et al. show that more TGF-β in the tumor environment is a chief mechanism for evading the immune system and that blockade of TGF-β acts in synergy with PD-L1 checkpoint blockade to induce tumor regression. In a mouse model of colorectal cancer, Tauriello et al. show that cancer-associated fibroblasts are the main contributors to TGF-β production and that a TGF-β inhibitor induces the enhanced infiltration of cytotoxic T cells and the TH1 subset of helper T cells into primary tumors and liver metastases. Mariathasan et al. show that in patients with metastatic urothelial cancer, a TGF-β-response signature in cancer-associated fibroblasts is associated with non-responsiveness to PD-L1 blockade in excluded tumors only, whereas tumor-mutational burden correlates with responsiveness in inflamed tumors only.