Single-cell CRISPR screens in vivo map T cell fate regulomes in cancer.

ABSTRACT: CD8⁺ cytotoxic T cells (CTLs) orchestrate antitumour immunity and exhibit inherent heterogeneity^1,2, with precursor exhausted T (T_pex) cells but not terminally exhausted T (T_ex) cells capable of responding to existing immunotherapies^3-7. The gene regulatory network that underlies CTL differentiation and whether T_ex cell responses can be functionally reinvigorated are incompletely understood. Here we systematically mapped causal gene regulatory networks using single-cell CRISPR screens in vivo and discovered checkpoints for CTL differentiation. First, the exit from quiescence of T_pex cells initiated successive differentiation into intermediate T_ex cells. This process is differentially regulated by IKAROS

SUBMITTER: Zhou P 

PROVIDER: S-EPMC10700132 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature