Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou, China.
Cancer Sci. 2021 Jan;112(1):144-154. doi: 10.1111/cas.14712. Epub 2020 Nov 17.
Eomesodermin (Eomes) is a T-box transcription factor that drives the differentiation and function of cytotoxic lymphocytes. However, the underlying function and mechanism of Eomes in tumor cells remains elusive. Here, we studied the role of Eomes in human esophageal squamous cell carcinoma (ESCC). Using 2 human ESCC cell lines, we found that Eomes knockdown reduced esophageal cancer cell proliferation and that the esophageal cancer cell cycle was blocked in the G2/M phase. Mechanistically, we identified CCL20 as the main downstream target of Eomes. Furthermore, we found that CCL20 could chemoregulate regulatory T cells (Tregs) through their specific receptor CCR6, then promoting the proliferation of esophageal cancer cells. Eomes knockdown also delayed the growth of human ESCC xenografts in BALB/c nude mice. Importantly, in 133 human ESCC tissues, high Eomes levels were associated with poor clinical prognosis. Overall, our findings suggested that the Eomes-CCL20-CCR6 pathway plays a vital role in human ESCC progress. Therefore, targeting this pathway may represent a promising strategy for controlling human ESCC.
Eomesodermin（Eomes）是一种 T 盒转录因子，可驱动细胞毒性淋巴细胞的分化和功能。然而，Eomes 在肿瘤细胞中的潜在功能和机制仍不清楚。在这里，我们研究了 Eomes 在人食管鳞癌（ESCC）中的作用。使用 2 个人 ESCC 细胞系，我们发现 Eomes 敲低减少了食管癌细胞的增殖，并且食管癌细胞周期被阻滞在 G2/M 期。在机制上，我们确定 CCL20 是 Eomes 的主要下游靶标。此外，我们发现 CCL20 可以通过其特异性受体 CCR6 对调节性 T 细胞（Tregs）进行化学调节，从而促进食管癌细胞的增殖。Eomes 敲低也延迟了 BALB/c 裸鼠人 ESCC 异种移植物的生长。重要的是，在 133 个人 ESCC 组织中，高水平的 Eomes 与不良的临床预后相关。总的来说，我们的研究结果表明，Eomes-CCL20-CCR6 通路在人 ESCC 进展中起着至关重要的作用。因此，靶向该通路可能代表控制人 ESCC 的一种有前途的策略。
