Targeting Nuclear Receptor Coactivator SRC-1 Prevents Colorectal Cancer Immune Escape by Reducing Transcription and Protein Stability of PD-L1.

ABSTRACT: Programmed death-ligand 1 (PD-L1) is overexpressed in multiple cancers and critical for their immune escape. It has previously shown that the nuclear coactivator SRC-1 promoted colorectal cancer (CRC) progression by enhancing CRC cell viability, yet its role in CRC immune escape is unclear. Here, we demonstrate that SRC-1 is positively correlated with PD-L1 in human CRC specimens. SRC-1 deficiency significantly inhibits PD-L1 expression in CRC cells and retards murine CRC growth in subcutaneous grafts by enhancing CRC immune escape via increasing tumor infiltration of CD8⁺ T cells. Genetic ablation of SRC-1 in mice also decreases PD-L1 expression in AOM/DSS-induced murine CRC. These results suggest that tumor-derived SRC-1 promotes CRC immune escape by enhancing PD-L1 expression

SUBMITTER: Hong Y 

PROVIDER: S-EPMC11434141 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature