Supporting data for "Mapping the dynamic intra-tumor ecosystem of esophageal squamous cell carcinoma at single-cell resolution"

Esophageal squamous cell carcinoma (ESCC) is characterized by poor clinical outcomes, which are partly attributable to intratumor heterogeneity and an immunosuppressive tumor microenvironment (TME). Single-cell transcriptomic profiling of paired tumor and adjacent normal tissues, along with matched blood samples from ESCC patients, was conducted to comprehensively characterize both tumor and systemic immune landscapes. The ESCC TME was found to be dominated by expanded immunosuppressive cell populations. Blood profiling identified circulating immune subsets associated with patient prognosis, indicating the potential utility of blood-based immune monitoring. Additionally, functional pathway analysis identified an NRF2-driven oxidative stress program in epithelial cells that is linked to therapeutic resistance. To assess the functional relevance of this pathway, NRF2 was depleted using lenti-CRISPR-Cas9, and subsequent functional assays were performed to evaluate tumor-related phenotypes. Collectively, these findings identify key immune and epithelial determinants of ESCC progression with potential prognostic and therapeutic significance.