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The tumour glyco-code as a novel immune checkpoint for immunotherapy

Abstract

Tumour growth is accompanied by tumour evasion of the immune system, a process that is facilitated by immune checkpoint molecules such as programmed cell death protein 1 (PD1). However, the role of tumour glycosylation in immune evasion has mostly been overlooked, despite the fact that aberrant tumour glycosylation alters how the immune system perceives the tumour and can also induce immunosuppressive signalling through glycan-binding receptors. As such, specific glycan signatures found on tumour cells can be considered as a novel type of immune checkpoint. In parallel, glycosylation of tumour proteins generates neo-antigens that can serve as targets for tumour-specific T cells. In this Opinion article, we highlight how the tumour 'glyco-code' modifies immunity and suggest that targeting glycans could offer new therapeutic opportunities.

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Figure 1: Glycosylation changes in cancer that connect to immune recognition.
Figure 2: The glyco-code in the tumour analysis of patients with cancer.
Figure 3: Therapeutic interventions that relate to the tumour glyco-code.

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Acknowledgements

The authors acknowledge support from the European Research Council (ERC-339977-Glycotreat; Y.v.K. and S.T.T.S.) and the European Union Horizon 2020 (Marie Skłodowska-Curie, Grant agreement No. 642870, and the European Training Network IMMUNOSHAPE (E.R.)). The authors thank the fruitful discussions with S. van Vliet, J. J. Garcia Vallejo and the contributions of our group-members that work on the immuno-glyco-code of cancer.

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Y.v.K. and E.R. researched data for the article, made substantial contributions to the discussion of content and wrote, reviewed and edited the manuscript before submission. S.T.T.S. researched data for the article and made substantial contributions to the discussion of content and the writing of the manuscript before submission.

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Correspondence to Yvette van Kooyk.

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RodrÍguez, E., Schetters, S. & van Kooyk, Y. The tumour glyco-code as a novel immune checkpoint for immunotherapy. Nat Rev Immunol 18, 204–211 (2018). https://doi.org/10.1038/nri.2018.3

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