GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE313nnn/GSE313246/suppl/filelist.txtftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE313nnn/GSE313246/suppl/GSE313246_RAW.tarftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE313nnn/GSE313246/primary200OKTranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE313246GEOGSEfalseCharacterization of Circulating Neoantigen-Specific T Cell Responses and Their Public TCR Repertoires in Lynch Syndrome Carriers (scTCRseq)Lynch syndrome (LS), a common hereditary cancer syndrome, provides a unique model to study immune surveillance at the earliest stages of tumorigenesis. A hallmark of LS carcinogenesis is the generation of highly immunogenic mutated neoantigens derived from insertion deletions, yet the transcriptomic states of the neoantigen-specific T cells that recognize them remain poorly characterized. Here, we characterized neoantigen-specific T cells from LS carriers using functional assays, single-cell RNA/TCR sequencing, and repertoire integration with existing data sets. Recurrent neoantigens elicited strong immune responses, with neoantigen-specific T cells mediating cytotoxicity against patient-derived tumor organoids. Single-cell analysis revealed oligoclonal expansions spanning effector and memory states with LS cancer survivors showing enrichment for metabolically exhausted subsets and previvor LS carriers retaining polyfunctional effectors. Cross-cohort analyses identified public clonotypes overlapping with tumor-infiltrating repertoire. These findings define the architecture of circulating neoantigen-specific immunity in LS and identify public TCRs as biomarkers for immune monitoring and immunoprevention.2026/08/13GSE313246GSM9364629GSM9364625GSM9364626GSM9364627GSM9364628GSM9364632GSM9364621GSM9364633GSM9364622GSM9364623GSM9364634GSM9364624GSM9364630GSM936463121290313246Homo sapiens