An important limitation of the Panc02 model is that these cells do not carry Kras mutations, which occur in 90% of human PDAC, but they are characterized by a loss-of-function mutation in the Smad4 gene occurring in 50% of human pancreatic cancers22; moreover, this cell line is derived from a methylcholanthrene-induced adenocarcinoma, resulting in many more mutations and neoantigens than human PDAC; however, they retain resistance to immune checkpoint blockade (ICB)23. This evidence concerns the gene SMAD4 and adenocarcinoma.