Stiftung Tierärztliche Hochschule Hannover (TiHo)

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

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 ORCID; Henrique, Rui M ORCID; Carneiro, Fátima ORCID; Dinis-Ribeiro, Mário ORCID; Marcos-Pinto, Ricardo; Lima, Margarida; Lepenies, Bernd GND; Sokol, Harry ORCID; Machado, José C ORCID; Vilanova, Manuel ORCID; Pinho, Salomé S

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.

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