- Berberine directly bound and inhibited CSN5 deubiquitylation activity → ↑ PD-L1 ubiquitylation and degradation → ↓ PD-L1 expression in cancer cells↑ IFN-γ and granzyme B production by CD8+ T cells↑ T cell activity and cytotoxicity of cancer cells↓ Treg & MSDCs numbers. The gene discussed is COPS5; the disease is cancer.