Nature Communications, Published online: 22 August 2026; doi:10.1038/s41467-026-76959-6 Responses to immune checkpoint inhibitors (ICI) in esophageal squamous cell carcinoma (ESCC) are highly heterogeneous, and the mechanisms underlying therapeutic sensitivity remain incompletely understood. Here the authors present multi-omics profiling of ESCC patients receiving neoadjuvant therapy and identify a CX3CR1⁺CD8⁺ T-cell cytotoxic effector state linked to response.