UPAR expression in M-MDSCs under high LDHA activity in pancreatic ductal adenocarcinoma.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an immunosuppressive tumor microenvironment (TME), which limits treatment efficacy. Lactate, produced from pyruvate by lactate dehydrogenase A (LDHA), is known to contribute to the formation of such an immunosuppressive TME. However, it remains unclear how lactate metabolism influences immune cell populations and contributes to immunosuppression under metabolic constraints in PDAC. To address this, we investigated the mechanisms by which a high-LDHA TME promotes an immunosuppressive landscape in PDAC using single-cell RNA sequencing and multiplex immunofluorescence staining. In a mouse Ldha-knockdown (shLdha) PDAC model characterized by reduced glucose consumption and lactate production, the number of myeloid-derived suppressor ce

SUBMITTER: Tsutsumi C 

PROVIDER: S-EPMC12769657 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature