Inhibiting WNT Ligand Production for Improved Immune Recognition in the Ovarian Tumor Microenvironment.

ABSTRACT: In ovarian cancer, upregulation of the Wnt/β-catenin pathway leads to chemoresistance and correlates with T cell exclusion from the tumor microenvironment (TME). Our objectives were to validate these findings in an independent cohort of ovarian cancer subjects and determine whether inhibiting the Wnt pathway in a syngeneic ovarian cancer murine model could create a more T-cell-inflamed TME, which would lead to decreased tumor growth and improved survival. We preformed RNA sequencing in a cohort of human high grade serous ovarian carcinoma subjects. We used CGX1321, an inhibitor to the porcupine (PORCN) enzyme that is necessary for secretion of WNT ligand, in mice with established ID8 tumors, a murine ovarian cancer cell line. In order to investigate the effect of decreased Wnt/β-catenin pa

SUBMITTER: Goldsberry WN 

PROVIDER: S-EPMC7140065 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature