α2,6-Sialylation promotes immune escape in hepatocarcinoma cells by regulating T cell functions and CD147/MMP signaling
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.
KeywordsST6Gal-I Immune escape T cell HCC CD147
Wang L. conceived and designed the study. Wang L., Li S., Yu X., Han Y., Wu Y., Wang S., and Chen X. performed the experiments. Wang L. and Li S. wrote the paper. Zhang J. and Wang S. reviewed and edited the manuscript. All authors read and approved the manuscript.
This research was supported by grants from the National Natural Science Foundation of China (No.31470799 and No.31570802), the Natural Science Foundation of Liaoning Province (No. 20170540288), and the Special Fund of Dalian city for Distinguished Young Scholars (2017RJ07).
Compliance with ethical standards
The study protocol conformed to the principles of the Declaration of Helsinki and was approved by the Ethics Committee of The First Affiliated Hospital of Dalian Medical University, Dalian City, P.R. China
Conflict of interest
The authors declare that they have no conflicts of interest.
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