Combining the antitumor efficiency of anti‐MSLN antibody plus neoantigen vaccine in two orthotopic pancreatic cancer model and the results of multiple immunofluorescences in human pancreatic cancer, showed that MSLN+ apCAFs in pancreatic cancer could significantly inhibit the infiltration of effector immune cells and correspondingly the combined treatment of αMSLN plus personalized neoantigen vaccine might serve as a feasible and effective strategy to improve immunotherapy of pancreatic cancer. Here, MSLN is linked to familial pancreatic carcinoma.