In this issue of the JCI, Redman et al. (8) describe the results of a phase 1b trial in patients with HPV-unrelated HNSCC, testing the neoadjuvant, presurgical administration of bintrafusp alfa, a bifunctional fusion protein that blocks PD-L1 and neutralizes TGF-β. This evidence concerns the gene TGFB1 and head and neck squamous cell carcinoma.