Remodeling of Stromal Immune Microenvironment by Urolithin A Improves Survival with Immune Checkpoint Blockade in Pancreatic Cancer.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a significant contributor to cancer-related morbidity and mortality, and it is known for its resistance to conventional treatment regimens, including chemotherapy and immune checkpoint blockade (ICB)-based therapies. We have previously shown that Urolithin A (Uro A), a gut microbial metabolite derived from pomegranates, can target and inhibit KRAS-dependent PI3K/AKT/mTOR signaling pathways to overcome therapeutic resistance and improve survival in PDAC. However, the effect of Uro A on the tumor immune microenvironment and its ability to enhance ICB efficacy has not been explored. This study demonstrates that Uro A treatment reduces stromal fibrosis and reinvigorates the adaptive T-cell immune response to overcome resistance to PD-1 blockade

SUBMITTER: Mehra S 

PROVIDER: S-EPMC10337606 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature