Interestingly Burke et al. demonstrated that ISG15 pathway knockdown not only reversed the KRAS-associated phenotypes of pancreatic ductal adenocarcinoma cells, such as increased proliferation and colony formation, but also decreased tumor programmed death ligand-1 (PDL-1) expression leading to increased number of CD8+ tumor-infiltrating lymphocytes [50]. This evidence concerns the gene KRAS and pancreatic ductal adenocarcinoma.