In an ESCC mouse model, NKP-1339/miR-142-NBs combined with ultrasound markedly suppressed tumor growth (79.72% ± 0.1% vs. NB control 18.79% ± 1.29%) through NKP-1339 triggering ICD and miR-142-5p down-regulating programmed death-ligand 1 (PD-L1) expression, synergistically potentiating immune responses. Here, CD274 is linked to esophageal squamous cell carcinoma.