A pan-immunotherapy signature to predict intratumoral CD8⁺ T cell expansions.

ABSTRACT: Effective cancer immunotherapy relies on the clonal proliferation and expansion of CD8⁺ T cells in the tumor. However, our insights into clonal expansions are limited, owing to an inability to track the same clones in tumors over time. Here, we develop a multi-site tumor mouse model system to track hundreds of expanding and contracting CD8⁺ T cell clones over multiple timepoints in tumors of the same individual. Through coupling of clonal expansion dynamics and single-cell RNA/TCR-seq data, we identify a transcriptomic signature in PD-1⁺Ly108⁺ precursor exhausted cells that strongly predicts rates of intratumoral clone expansion. The signature correlates with expansion in mice, both with and without immunotherapies, and in patients undergoing PD-

SUBMITTER: Takahashi M 

PROVIDER: S-EPMC12537911 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature