Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian, 116044, China.
School of Life Science and Medicine, Dalian University of Technology, Panjin, 124221, Liaoning, China.
J Physiol Biochem. 2019 Jun;75(2):199-207. doi: 10.1007/s13105-019-00674-8. Epub 2019 Apr 10.
Altered glycosylation is a common feature of cancer cells and plays an important role in tumor progression. β-Galactoside α2-6-sialyltransferase 1 (ST6Gal-I) is the critical sialyltransferase responsible for the addition of α2-6-sialic acid to the terminal N-glycans on the cell surface. However, the functions and mechanism of ST6Gal-I in tumor immune escape remain poorly understood. Here, we found that ST6Gal-I overexpression promoted hepatocarcinoma cell proliferation, migration, and immune escape by increasing the levels of CD147, MMP9, MMP2, and MMP7. When CD8 T cells were co-cultured with cell lines expressing different levels of ST6Gal-I, we found that ST6Gal-I upregulation inhibited the T cell proliferation and increased the secretion of IL-10 and TGF-β1, while secretion of IFN-γ and TNF-α was diminished. In a syngeneic tumor transplant model, ST6Gal-I upregulated Hca-P. In addition, Hepa1-6 cells formed significantly larger tumors and suppressed intratumoral penetration by CD8 T cells. In combination, these results suggest that ST6Gal-I promotes the immune escape of hepatocarcinoma cells in the tumor microenvironment and highlight the importance of assessing ST6Gal-I status for immunotherapies.
糖基化改变是癌细胞的一个常见特征，在肿瘤进展中起着重要作用。β-半乳糖苷α2-6-唾液酸转移酶 1（ST6Gal-I）是负责在细胞表面末端 N-糖链上添加α2-6-唾液酸的关键唾液酸转移酶。然而，ST6Gal-I 在肿瘤免疫逃逸中的功能和机制仍知之甚少。在这里，我们发现 ST6Gal-I 的过表达通过增加 CD147、MMP9、MMP2 和 MMP7 的水平，促进肝癌细胞的增殖、迁移和免疫逃逸。当 CD8 T 细胞与表达不同 ST6Gal-I 水平的细胞系共培养时，我们发现 ST6Gal-I 的上调抑制了 T 细胞的增殖，并增加了 IL-10 和 TGF-β1 的分泌，而 IFN-γ 和 TNF-α 的分泌则减少。在同种异体肿瘤移植模型中，ST6Gal-I 上调了 Hca-P。此外，Hepa1-6 细胞形成的肿瘤明显更大，并抑制了 CD8 T 细胞在肿瘤内的浸润。总之，这些结果表明 ST6Gal-I 促进了肿瘤微环境中肝癌细胞的免疫逃逸，并强调了评估 ST6Gal-I 状态对于免疫治疗的重要性。
