Meng Hui, Ding Yi, Liu Enjie, Li Wencai, Wang Liang
Department of Pathology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Pathology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
Transl Oncol. 2021 Feb;14(2):101003. doi: 10.1016/j.tranon.2020.101003. Epub 2020 Dec 25.
CRC is a heterogeneous disease due to global molecular alterations, including mismatch-repair-deficient (dMMR) and microsatellite instability-high (MSI-H). Immunotherapy has achieved durable responses in a subset of patients with dMMR-MSI-H metastatic CRC. It has been showed that Loss of ZG16 is highly associated with colorectal cancer. However, whether ZG16 modulates tumor immunity in colorectal cancer is unclear. In this study, we demonstrated that the expression of ZG16 is associated with distant metastasis and lymphatic invasive in colorectal cancer. Besides, ZG16 is negatively correlated to PD-L1 expression in patient with CRC and overexpression of ZG16 blocks PD-L1 expression in colorectal cancer cells. In addition, overexpression of ZG16 promotes NK cells survival and proliferation, which is dependent on NKG2D expression. Our data demonstrate that ZG16 plays a role in modulation of immune response in colorectal cancer. The strong correlation between ZG16 and PD-L1 suggests that ZG16 may serve a biomarker to stratify patient who will benefit from immunotherapy.
由于包括错配修复缺陷（dMMR）和微卫星高度不稳定（MSI-H）在内的整体分子改变，结直肠癌是一种异质性疾病。免疫疗法在一部分dMMR-MSI-H转移性结直肠癌患者中取得了持久疗效。研究表明，ZG16缺失与结直肠癌高度相关。然而，ZG16是否调节结直肠癌的肿瘤免疫尚不清楚。在本研究中，我们证明ZG16的表达与结直肠癌的远处转移和淋巴浸润相关。此外，在结直肠癌患者中，ZG16与PD-L1表达呈负相关，ZG16过表达可阻断结直肠癌细胞中PD-L1的表达。此外，ZG16过表达促进NK细胞存活和增殖，这依赖于NKG2D表达。我们的数据表明ZG16在调节结直肠癌免疫反应中发挥作用。ZG16与PD-L1之间的强相关性表明，ZG16可能作为一种生物标志物，用于对将从免疫疗法中获益的患者进行分层。
