Iron-overload affects anti-tumor immune response in pancreatic cancer.

Abstract HFE is the most frequently mutated gene in hereditary hemochromatosis, a disease which iron accumulates organs leading to toxicities. Worldwide, two main polymorphisms protein have been observed, namely C282Y and H63D. Even if associated milder accumulations, H63D polymorphism increases risk of cancer development aggressiveness. As observed pancreatic patients, great percentage those that underwent surgery also present but displayed worse survival. To better characterize how accumulation affects anti-tumor response context ductal adenocarcinoma (PDA), we crossed genetically engineered mice (GEM) spontaneously develop PDA with express H67D mutation (HfeH67D), orthologue human. Histological analysis GEM showed accelerated progression, increased number metastases, altered composition infiltrating immune cells. Accordingly, these mouse models reduced overall survival compared controls. By exploiting OVA as well-known antigen, injected OVA-expressing cells subcutaneously carrying or not assess their ability mount normal memory response. grew faster presence polymorphism, immunized reduction tumor volume similar WT counterpart. HfeH67Dmice an production anti-OVA IgG antibodies, especially IgE, decreased OVA-specific IFNγ-secreting T Overall, impacts activation anti-tumoral response, consequently worsens progression. Supported by grants from AIRC (ID22234; ID26341)