In summary, we identified a tRF‐22–hnRNPAB–TGFβ2–PMN‐MDSCs–CD8+ T cell pathway that illustrates the formation of the immunosuppressive TME in ESCC, providing a novel mechanism‐based candidate strategy for combination therapy to overcome ICB resistance in ESCC. Here, CD8A is linked to esophageal squamous cell carcinoma.