CD274 (programmed death ligand 1, PD-L1) is an immune checkpoint protein that functions as a critical negative regulator of anti-tumor immunity. CD274 binds to programmed death receptor 1 (PDCD1/PD-1) on T lymphocytes, inhibiting T cell proliferation and cytotoxic effector function 1. This interaction suppresses anti-tumor immunity, allowing cancer cells to evade immune destruction 23. CD274 undergoes degradation through proteasomal and lysosomal pathways; baicalein, a natural compound, promotes CD274 autophagic degradation by enhancing interaction with MAP1LC3B, thereby boosting T cell-mediated anti-tumor immunity 4. CD274 expression is regulated by viral and cellular mechanisms; KSHV K-RTA protein transactivates the CD274 promoter through cooperation with transcription factor SP1 5. MerTK-mediated macrophage efferocytosis increases CD274 expression via the p38/STAT3 pathway, promoting immune tolerance 6. Clinically, CD274 polymorphisms associate with cancer susceptibility; specific variants modulate lung cancer and systemic lupus erythematosus risk in different populations 78. Blocking the CD274-PDCD1 pathway reverses T cell exhaustion and normalizes anti-tumor responses, providing the therapeutic rationale for immune checkpoint inhibitors in cancer treatment 9.