Hundeyin, Kurz, and colleagues discovered that innate αβ T cells (iαβT) were a substantial part of the T-lymphocyte population in human and mouse pancreatic ductal adenocarcinoma (PDA) tumors. These tumor-infiltrating iαβTs were highly activated, had a phenotype markedly different from those in the periphery, and were protective against PDA progression in mice. Demonstrating the relevance of these findings to human disease, treatment of patient-derived organotypic PDA tumor spheroids with autologous iαβTs led to conventional T-cell activation. The mechanism involved activation of CCR5, which induced immunogenic macrophage polarization. Collectively, these findings suggest that iαβT-based cell therapies should be investigated for the treatment of PDA. For details, please see the article by Hundeyin, Kurz, and colleagues on page 1288.