A Genome-wide CRISPR Screen on T Cell Function

Very excited to share our recent work on a genome-wide CRISPR screen focusing on regulation of T cell function.

http://www.pnas.org/content/early/2018/04/03/1801340115.short

Significance

Recent success of T cell-based cancer immunotherapies highlights the importance of further understanding molecular mechanisms in the regulation of T cell responsiveness. Here, we performed a genome-wide CRISPR screen to identify genes that regulate T cell activation upon anti-T cell receptor (TCR) stimulation. Our screen confirmed many of the known regulators in proximal T cell signaling. Moreover, we identified a previously uncharacterized gene named FAM49B, which acts as a negative regulator in T cell activation. Our study suggests that genome-wide CRISPR screening is a powerful means to identify key regulators of TCR signaling. The same strategy could be applied to CD28-mediated costimulatory signaling or PD-1–mediated coinhibitory signaling. The unbiased approach presented here may allow us to identify new therapeutic targets for cancer immunotherapy.