Single-Cell Clonal Lineage Tracing Identifies the Transcriptional Program Controlling the Cell-Fate Decisions by Neoantigen-Specific CD8+ T Cells.

ABSTRACT: Neoantigen-specific T cells recognize tumor cells and are critical for cancer immunotherapies to be effective. However, the transcriptional program controlling the cell fate decisions by neoantigen-specific T cells is incompletely understood. In this study, using joint single-cell transcriptome and T-cell receptor profiling, we mapped the clonal expansion and differentiation of neoantigen-specific CD8+ T cells in the tumor and draining lymph node (LN) in mouse prostate cancer. Neoantigen-specific CD8+ tumor-infiltrating lymphocytes upregulated gene signatures of T-cell activation and exhaustion compared with those recognizing other tumor antigens. In the tumor-draining LN, we identified TCF1+TOX- stem cell memory T cells (TSCM), TCF1+TOX+ progenitor exhausted T cells (TPEX), and TCF1-TOX+

SUBMITTER: Luo Y 

PROVIDER: S-EPMC12611225 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature