Here we use mouse- and human-derived autologous pancreatic cancer organoid/immune cell co-cultures and orthotopic transplant mouse model of PDAC to demonstrate that elevated infiltration of polymorphonuclear (PMN)-MDSCs within the PDAC tumor microenvironment inhibit T cell effector function, regardless of PD-1/PD-L1 inhibition. This evidence concerns the gene PDCD1 and familial pancreatic carcinoma.