Glycans as Immune Checkpoints: Removal of Branched N-glycans Enhances Immune Recognition Preventing Cancer Progression

Tumor growth is accompanied with dramatic changes in the cellular glycome, such as the aberrant expression of complex branched N-glycans. However, the role of this protumoral N-glycan in immune evasion and whether its removal contributes to enhancement of immune recognition and to unleashing an anti...

Full description

Saved in:
Bibliographic Details
Published in:Cancer immunology research 2020-11, Vol.8 (11), p.1407-1425
Main Authors: Silva, Mariana C, Fernandes, Ângela, Oliveira, Maria, Resende, Carlos, Correia, Alexandra, de-Freitas-Junior, Julio C, Lavelle, Aonghus, Andrade-da-Costa, Jéssica, Leander, Magdalena, Xavier-Ferreira, Helena, Bessa, José, Pereira, Carina, Henrique, Rui M, Carneiro, Fátima, Dinis-Ribeiro, Mário, Marcos-Pinto, Ricardo, Lima, Margarida, Lepenies, Bernd, Sokol, Harry, Machado, José C, Vilanova, Manuel, Pinho, Salomé S
Format: Article
Language:English
Subjects:
Cancer
Life Sciences
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Tumor growth is accompanied with dramatic changes in the cellular glycome, such as the aberrant expression of complex branched N-glycans. However, the role of this protumoral N-glycan in immune evasion and whether its removal contributes to enhancement of immune recognition and to unleashing an antitumor immune response remain elusive. We demonstrated that branched N-glycans are used by colorectal cancer 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 colorectal cancer, highlighting the therapeutic efficacy of its deglycosylation to potentiate immune recognition and, thus, improving cancer immunotherapy.
ISSN:2326-6066
2326-6074
DOI:10.1158/2326-6066.CIR-20-0264