In contrast, the immune exhaustion hallmarks, that is, multiple co‐expressed checkpoints and costimulatory markers56 (e.g. CTLA4‐TIGIT and HAVCR2‐PDCD1 co‐expression representing severely exhausted state57) was obvious in CD8+ T cells of ESCC but inconspicuous in HIN (Figure 6B, Figure S12). Here, CTLA4 is linked to esophageal squamous cell carcinoma.