Tumor immune microenvironment in pancreatic ductal adenocarcinoma revisited – Exploring the “Space”

regulatory T-cells, play a key role in immune regulation, yet PDAC is largely an immunologically "cold" tumour with limited effector T-cell infiltration. The surrounding cellular microenvironment, particularly Cancer Associated Fibroblasts (CAFs) and macrophages, contributes to immune evasion by promoting a fibrotic and desmoplastic barrier that limits TIL infiltration. The prognostic significance of TILs is increasingly recognized, with higher densities correlating with improved survival, whereas regulatory T-cell infiltration and immunosuppressive stromal interactions are associated with poor outcomes. Emerging therapeutic strategies targeting the TIME (e.g., CAFs), immune checkpoint inhibitors, and TIL-based therapies offer the potential to overcome resistance. Future research must focus on optimizing immunotherapy strategies and unravelling the complex stromal-immune interactions to improve clinical translation.