Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China.
Beijing Key Lab for Immunological Research on Chronic Diseases, Beijing, China.
Front Immunol. 2018 Dec 18;9:2981. doi: 10.3389/fimmu.2018.02981. eCollection 2018.
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-1Tim-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 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 . 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.
Eomes 是 T 盒转录因子，已知对效应器和记忆 T 细胞的功能和稳态很重要，但最近也与 CD8 T 细胞耗竭有关。然而，Eomes 是否以及如何调节 CD8 T 细胞的效应功能或耗竭，特别是在肿瘤环境中，尚不清楚。在这里，我们首先表明，随着肿瘤的进展，肿瘤浸润性 CD8 T 细胞中 Eomes 的表达升高，尤其是在 PD-1Tim-3 耗竭的 CD8 T 细胞中。T 细胞中 Eomes 的完全缺失导致抗肿瘤 CTL 的发育受损，而 T 细胞中 的一个等位基因缺失会减少耗竭的 CD8 T 细胞的发育，从而更好地控制肿瘤。对 Eomes 过表达 T 细胞的 RNAseq 和 ChIPseq 的综合分析表明，高水平的 Eomes 表达直接控制 T 细胞耗竭基因的表达，如 。此外，Eomes 可能与 T-bet 竞争结合调节基因组位点点来拮抗 T-bet 的功能。总之，Eomes 在肿瘤中的 CD8 T 细胞中发挥双重作用。
