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Immunotherapy using antibodies blocking the programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway has achieved great success in preclinical models and the clinical treatment of esophageal squamous cell carcinoma (ESCC). The c-Myc proto-oncogene helps prevent immune cells from attacking tumor cells by inducing PD-L1 expression. However, the underlying mechanisms of c-Myc and PD-L1 in ESCC remain unclear, and a thorough understanding of this regulation would allow the development of new approaches to enhance antitu