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 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.