CD274 (programmed death ligand 1, PD-L1) is an immune checkpoint protein that binds to PDCD1 (PD-1) on T lymphocytes to inhibit cytotoxic T cell effector function and promote tumor immune evasion. Tumors exploit this PDCD1-mediated inhibitory pathway to attenuate anti-tumor immunity and facilitate survival. Blocking CD274–PDCD1 interaction reverses exhausted T-cell phenotypes and restores anti-tumor responses, establishing the rationale for immune checkpoint inhibitor therapy 1. Multiple FDA-approved monoclonal antibodies targeting CD274—including atezolizumab, avelumab, durvalumab, and envafolimab—have transformed cancer treatment across solid tumors and hematologic malignancies, though response rates remain limited to approximately 25–30% of patients in most indications 2. Recent evidence suggests that CD274 protein undergoes degradation via proteasomal and lysosomal pathways, and emerging strategies promote CD274 degradation through autophagy-targeting compounds to enhance immunotherapy efficacy 3. Beyond cancer, CD274 polymorphisms and genetic alterations associate with systemic lupus erythematosus susceptibility in the Chinese Han population 4 and contribute to thyroid MALT lymphoma pathogenesis, where CD274 inactivation may dysregulate T-cell help to malignant B-cells 5. CD274 expression by eosinophils also plays a role in asthma pathogenesis 6.