| First Author | Zhao H | Year | 2021 |
| Journal | Cell Rep | Volume | 37 |
| Issue | 10 | Pages | 110083 |
| PubMed ID | 34879274 | Mgi Jnum | J:347542 |
| Mgi Id | MGI:6883805 | Doi | 10.1016/j.celrep.2021.110083 |
| Citation | Zhao H, et al. (2021) Genome-wide fitness gene identification reveals Roquin as a potent suppressor of CD8 T cell expansion and anti-tumor immunity. Cell Rep 37(10):110083 |
| abstractText | Robust expansion of adoptively transferred T cells is a prerequisite for effective cancer immunotherapy, but how many genes in the genome modulate T cell expansion remains unknown. Here, we perform in vivo and in vitro CRISPR screens to systematically identify genes influencing CD8 T cell expansion. In the mouse genome, approximately 2,600 and approximately 1,500 genes are required for optimal CD8 T cell expansion in vivo and in vitro, respectively. In vivo-specific CD8 T cell essential genes are enriched in metabolic pathways, including mitochondrial metabolism. The strongest repressor of CD8 T cell expansion is Roquin, the ablation of which drastically boosts T cell proliferation by enhancing cell-cycle progression and upregulation of IRF4. Roquin deficiency or IRF4 overexpression potently enhances anti-tumor immunity. These data provide a functional catalog of CD8 T cell fitness genes and suggest that targeting the Roquin-IRF4 axis is an effective strategy to enhance efficacy of adoptive transfer therapy for cancer. |
