Targeting Prolyl 3-hydroxylase 1 Inhibits Pancreatic Cancer Progression and Macrophage Immunity

Using transcriptome sequencing, proteomic analyses and engineered mouse model, we have revealed a novel and pivotal role of Prolyl 3-hydroxylase 1 (P3H1) in PDAC. The expression of P3H1 is elevated in PDAC and correlates with poor outcomes in human patients. The genetic deletion of P3H1 in KPC mouse model (LSL-Kras G12D/+;Trp53loxP/loxP;Pdx1-Cre) significantly delays PDAC progression and alters immunosuppressive microenvironment, thereby prolonging mice survival.Our findings reveal a novel P3H1 target in PDAC progression and suggest a promising therapeutic strategy for PDAC treatment.