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, 2021 12 07.
Article
in En
| MEDLINE
| ID: mdl-34879274
ABSTRACT
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, â¼2,600 and â¼1,500 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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Lymphocyte Activation
/
Immunotherapy, Adoptive
/
CD8-Positive T-Lymphocytes
/
Cytotoxicity, Immunologic
/
Ubiquitin-Protein Ligases
/
Cell Proliferation
/
Neoplasms
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Cell Rep
Year:
2021
Type:
Article
Affiliation country:
China