Therefore, while our quantitative analysis highlighted CD4+ Tem as a key differential subset, future studies should incorporate functional markers such as Programmed Cell Death Protein 1 (PD-1), T Cell Immunoglobulin and Mucin-Domain Containing-3 (TIM-3), and Granzyme B (GZMB) to explore the roles of CD4+ Tem and CD8+ Tem in the TM4SF-defined ESCC subtype (73–75), which may reveal immune escape mechanisms beyond changes in cell infiltration numbers. This evidence concerns the gene GZMB and esophageal squamous cell carcinoma.