Optimizing CAR T cell therapy in pancreatic cancer through clinically actionable combinations

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most refractory malignancies to immunotherapy, owing to physical and immunologic barriers that collectively limit the efficacy of T cell-based approaches, including chimeric antigen receptor (CAR) T cell therapies. In PDAC, a dense desmoplastic stroma restricts T cell infiltration, while immunosuppressive factors derived from tumor cells, stromal components, and regulatory immune populations (i.e., regulatory T cells and suppressive myeloid cells) actively impair T cell function.