In this work, we reveal a dynamic immune landscape in esophageal squamous cell cancer (ESCC) mediated by TLSs through spatial proteomics using imaging mass cytometry (IMC), highlighted by the distinct distribution patterns of TCF-1+ subsets within intratumoral CD39+CD8+ Tex cells, which are closely associated with clinical benefits from ICB therapy. This evidence concerns the gene ENTPD1 and esophageal squamous cell carcinoma.