In our study, several genetic clues implied that this ESCC subgroup might respond to ICIs: (1) higher TMB; (2) active infiltrations of immune cells, especially CD8+ T cells, which were predictive of ICIs; (3) higher expression of an IFN-γ–related signature, which was confirmed as a predictor of responses to pembrolizumab in KEYNOTE-012 and KEYNOTE-028 (40); and (4) high similarity of the FAT/FRY ESCC expression profile to those of ICI responders. The gene discussed is IFNG; the disease is esophageal squamous cell carcinoma.