CD274 and neoplasm: Nevertheless, three unresolved scientific issues hinder progress (1): Heterogeneous therapeutic responses limit durable clinical benefits to 20–50% of patients (5) (2); Immune-related adverse events (irAEs) affect nearly half of the treated individuals (incidence: 43%) (6) (3); Existing predictive biomarkers, including PD-L1 expression and tumor mutational burden, exhibit suboptimal specificity for identifying true responders (7).