{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE314nnn/GSE314906/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE314906"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"CX3CR1⁺ CD8⁺ Cytotoxic T Cells Drive Tumor Killing in Esophageal Squamous Cell Carcinoma During Neoadjuvant Therapy","description":"The efficacy of immune checkpoint blockade (ICB) in esophageal squamous cell carcinoma (ESCC) remains highly variable, and the underlying mechanisms driving differential responses are poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq), T cell receptor (TCR) sequencing, and whole exome sequencing (WES) on 52 ESCC patients from a phase III neoadjuvant clinical trial to characterize the tumor microenvironment (TME) and its association with therapeutic outcomes. We identified a selective expansion of non-exhausted cytotoxic CD8⁺ T cells, particularly CX3CR1⁺ CD8⁺ T cells, in well responders, driven by the CX3CL1-CX3CR1 axis. These cells exhibited high cytotoxicity, clonal expansion, and tumor-killing potential, while exhausted T cell subsets, including CXCL13⁺ CD8⁺ T cells, were reduced in well responders. Pre-treatment tumor mutational profiles revealed that a high cancer cell fraction (CCF) mutation burden and neoantigen abundance were predictive of response, with immune editing reducing immunogenic mutations post-treatment. Additionally, tumor epithelial differentiation (Gp1/Gp2 subtypes) and stromal remodeling influenced treatment outcomes, with Gp2 tumors associated with immune suppression and resistance. Our findings provide new insights into the immune dynamics of ESCC, highlighting CX3CR1⁺ CD8⁺ T cells, the CX3CL1-CX3CR1 axis, and tumor differentiation as potential therapeutic targets to enhance ICB efficacy.","dates":{"publication":"2026/08/10"},"accession":"GSE314906","cross_references":{"GSM":["GSM9416037","GSM9416036","GSM9416079","GSM9416035","GSM9416034","GSM9416078","GSM9416039","GSM9416038","GSM9416073","GSM9416072","GSM9416071","GSM9416070","GSM9416077","GSM9416033","GSM9416076","GSM9416032","GSM9416031","GSM9416075","GSM9416074","GSM9416030","GSM9416048","GSM9416047","GSM9416046","GSM9416045","GSM9416049","GSM9416009","GSM9416080","GSM9416040","GSM9416084","GSM9416083","GSM9416082","GSM9416081","GSM9416088","GSM9416044","GSM9416043","GSM9416087","GSM9416086","GSM9416042","GSM9416085","GSM9416041","GSM9416059","GSM9416015","GSM9416014","GSM9416058","GSM9416057","GSM9416013","GSM9416056","GSM9416012","GSM9416019","GSM9416018","GSM9416017","GSM9416016","GSM9946389","GSM9416051","GSM9416050","GSM9416011","GSM9416055","GSM9416054","GSM9416010","GSM9416053","GSM9416052","GSM9416026","GSM9416025","GSM9416069","GSM9416068","GSM9416024","GSM9416023","GSM9416067","GSM9416029","GSM9416028","GSM9416027","GSM9416062","GSM9416061","GSM9416060","GSM9416066","GSM9416022","GSM9416065","GSM9416021","GSM9416020","GSM9416064","GSM9416063"],"GPL":["11154"],"GSE":["314906"],"taxon":["Homo sapiens"]}}