The study addresses the challenges of poor treatment responses in pancreatic ductal adenocarcinoma (PDAC) due to tumor heterogeneity and an immunosuppressive tumor microenvironment (TME). It introduces the InterOMaX model system, a 3D co-culture platform that mimics matrix-dependent cellular crosstalk to investigate T cell responses in PDAC. This system uses a customizable matrix and organoid-in-matrix positioning to co-culture PDAC cells with T cells and stromal cells. By detecting and analyzing PDAC cell populations with varying sensitivity to T cell killing, the platform enables identification and validation of gene candidates for T cell resistance, advancing the understanding of cancer cell-intrinsic resistance phenotypes in PDAC.

Keywords: Pancreatic cancer organoid, T-cell killing, pancreatic ductal adenocarcinoma, tumor microenvironment