Fig. 8

Mechanism proposed to illustrate the PD-L1 increase in drug-resistant A549/CDDP, MCF7/ADR and HepG2/ADR cells. In these drug-resistant cancer cells, decreased levels of the E3 ligase COP1 inhibit c-Jun ubiquitination, which decreases degradation and thereby increases c-Jun accumulation. Then, the increased c-Jun is phosphorylated by JNK and translocated into the nucleus to inhibit HDAC3 expression, which subsequently induces histone H3 acetylation of the PD-L1 promoter. The increased acetylation facilitates PD-L1 transcription and thus increases PD-L1 expression, which suppresses CD3⁺ T cells by interacting with PD-1