Sequential modulation of the Wnt/β-catenin signaling pathway enhances tumor-intrinsic MHC I expression and tumor clearance.

ABSTRACT:

Background

Progress in immunotherapy use for gynecologic malignancies is hampered by poor tumor antigenicity and weak T cell infiltration of the tumor microenvironment (TME). Wnt/β-catenin pathway modulation demonstrated patient benefit in clinical trials as well as enhanced immune cell recruitment in preclinical studies. The purpose of this study was to characterize the pathways by which Wnt/β-catenin modulation facilitates a more immunotherapy-favorable TME.

Methods

Human tumor samples and in vivo patient-derived xenograft and syngeneic murine models were administered Wnt/β-catenin modulating agents DKN-01 and CGX-1321 individually or in sequence. Analytical methods included immunohistochemistry, flow cytometry, multiplex cytokine/chemokine array, and RNA sequencing.

Re

SUBMITTER: Dholakia J 

PROVIDER: S-EPMC9105159 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature