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α2,6-Sialylation promotes immune escape in hepatocarcinoma cells by regulating T cell functions and CD147/MMP signaling

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A Correction to this article was published on 01 November 2019

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Abstract

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.

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Change history

  • 03 December 2019

    Subsequently to the publication of this article, the authors have noticed that the published version of Fig. 4H contained incorrect data showing the migration of the Mock cells (left panel, Hepa1-6 cells transfected with pcDNA3.1).

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Funding

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).

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Author notes

  1. Liping Wang and Shijun Li contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian, 116044, China

    Liping Wang, Yang Han, Yinshuang Wu, Shidan Wang & Shujing Wang

  2. School of Life Science and Medicine, Dalian University of Technology, Panjin, 124221, Liaoning, China

    Liping Wang, Xixi Chen & Jianing Zhang

  3. Department of inspection, First Affiliated Hospital of Dalian Medical University, Dalian, 116011, Liaoning Province, China

    Shijun Li

  4. Department of Pathology, Dalian Medical University, Dalian, 116044, Liaoning Province, China

    Xiao Yu

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  1. Liping Wang
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  3. Xiao Yu
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  4. Yang Han
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Contributions

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.

Corresponding authors

Correspondence to Jianing Zhang or Shujing Wang.

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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

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The authors declare that they have no conflicts of interest.

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Wang, L., Li, S., Yu, X. et al. α2,6-Sialylation promotes immune escape in hepatocarcinoma cells by regulating T cell functions and CD147/MMP signaling. J Physiol Biochem 75, 199–207 (2019). https://doi.org/10.1007/s13105-019-00674-8

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