| First Author | Li J | Year | 2018 |
| Journal | Front Immunol | Volume | 9 |
| Pages | 2981 | PubMed ID | 30619337 |
| Mgi Jnum | J:295062 | Mgi Id | MGI:6459604 |
| Doi | 10.3389/fimmu.2018.02981 | Citation | Li J, et al. (2018) High Levels of Eomes Promote Exhaustion of Anti-tumor CD8(+) T Cells. Front Immunol 9:2981 |
| abstractText | Eomes, a T-box transcription factor, is known important for both function and homeostasis of effector and memory T cells, but was recently also implicated in CD8(+) T cell exhaustion. However, whether and how Eomes might regulate effector functions or exhaustion of CD8(+) T cells, especially in the tumor setting, is unknown. Here we first show, as tumor progressed, Eomes expression was elevated in tumor-infiltrating CD8(+) T cells, especially in PD-1(+)Tim-3(+) exhausted CD8(+) T cells. Complete loss of Eomes in T cells resulted in impaired development of anti-tumor CTLs, whereas deletion of one allele of Eomes in T cells decreased development of exhausted CD8(+) T cells, which offered better tumor control. Integrative analysis of RNAseq and ChIPseq of Eomes-overexpressing T cells revealed that high levels of Eomes expression directly controlled expression of T cell exhaustion genes, such as Havcr2. In addition, Eomes might compete with T-bet binding to regulatory genomic loci to antagonize T-bet functions. Collectively, Eomes exerts bimodal functions in CD8(+) T cells in tumor. |
