STK25 Loss Augments Anti-PD-1 Therapy Efficacy by Regulating PD-L1 Stability in Colorectal Cancer.

ABSTRACT: Tumor immune evasion is intricately linked to malignant tumor progression and contributes to the failure of anti-cancer immunotherapy. Serine/threonine protein kinase 25 (STK25) has been previously implicated in the progression of various neoplastic diseases. However, the function of STK25 in the colorectal cancer (CRC) microenvironment remains unclear. Here, it is demonstrated that STK25 global knockout (STK25^-/-) mice and STK25-knockout tumor-bearing mice exhibited enhanced effectiveness of anti-PD-1 immunotherapy, which leads to significant tumor suppression with increased recruitment of CD8⁺ T cells. Mechanistically, STK25 deficiency increased PD-L1 protein levels by regulating PD-L1 K48-linked ubiquitination in a NEDD4-dependent manner. Moreover, CRC patients wit

SUBMITTER: Qiao X 

PROVIDER: S-EPMC12533155 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature