{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE335nnn/GSE335480/"]},"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=GSE335480"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Single-cell tracking reveals tumor-reactive T cell plasticity during melanoma TIL therapy","description":"Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) can induce durable responses in metastatic melanoma, yet the clonal and transcriptional dynamics that govern tumor-reactive T cell fate during ex vivo expansion and after transfer remain poorly understood. Here, we performed longitudinal single-cell RNA and T cell receptor (TCR) sequencing across five timepoints, from baseline tumors through a two-phase ex vivo expansion to post-infusion peripheral blood and tumor biopsies, in seven melanoma patients, generating a high-resolution map of both CD8+ and CD4+ tumor-reactive T cell plasticity. During early expansion (preREP), tumor-reactive CD8+ T cells were reinvigorated from an exhausted state and acquired distinct HLA-II-high or KLF2-high transcriptional profiles. In-depth characterization of the CD4+ compartment revealed lineage-dependent reinvigoration. After transfer, both CD8+ and CD4+ tumor-reactive clones acquired stem-like profiles and tissue-homing markers before re-infiltrating tumor lesions. Mechanistically, we identify two processes linked to treatment failure in non-responders: de novo expansion of immunosuppressive regulatory T cells, and co-transfer of Type 17 T cells. These data provide a comprehensive longitudinal framework of T cell plasticity during TIL-ACT.","dates":{"publication":"2026/07/10"},"accession":"GSE335480","cross_references":{"GSM":["GSM9814386","GSM9814387","GSM9814384","GSM9814385","GSM9814382","GSM9814383","GSM9814380","GSM9814381","GSM9814405","GSM9814406","GSM9814403","GSM9814404","GSM9814401","GSM9814402","GSM9814388","GSM9814389","GSM9814400","GSM9814409","GSM9814407","GSM9814408","GSM9814390","GSM9814397","GSM9814398","GSM9814395","GSM9814396","GSM9814393","GSM9814394","GSM9814391","GSM9814392","GSM9814416","GSM9814414","GSM9814415","GSM9814379","GSM9814412","GSM9814413","GSM9814399","GSM9814410","GSM9814411"],"GPL":["24676"],"GSE":["335480"],"taxon":["Homo sapiens"]}}