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Glycans as immune checkpoints : removal of branched N-glycans enhances immune recognition preventing cancer progression

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Lepenies,  Bernd
Bernd Lepenies, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Citation

Silva, M. C., Fernandes, Â., Oliveira, M., Resende, C., Correia, A., de-Freitas-Junior, J. C. M., et al. (2020). Glycans as immune checkpoints: removal of branched N-glycans enhances immune recognition preventing cancer progression. Cancer Immunology Research, 8(11), 1407-1425. doi:10.1158/2326-6066.CIR-20-0264.


Cite as: http://hdl.handle.net/21.11116/0000-0007-0F43-E
Abstract
Tumor growth is accompanied with dramatic changes in the cellular glycome, such as the aberrant expression of complex branched N-glycans. However, it remains elusive the role of this pro-tumoral N-glycan in immune evasion and whether its removal contributes to enhancement of immune recognition and to unleash an antitumor immune response. We demonstrated that branched N-glycans are used by colorectal cancer (CRC) cells to escape immune recognition, instructing the creation of immunosuppressive networks through inhibition of IFNγ. The removal of this "glycan-mask" exposed immunogenic mannose glycans that potentiated immune recognition by DC-SIGN-expressing immune cells, resulting in an effective antitumor immune response. We revealed a glycoimmune checkpoint in CRC, highlighting the therapeutic efficacy of its deglycosylation to potentiate immune recognition and, thus, improving cancer immunotherapy.