posted on 2023-04-04, 01:04authored byMariana C. Silva, Ângela Fernandes, Maria Oliveira, Carlos Resende, Alexandra Correia, Julio C. de-Freitas-Junior, Aonghus Lavelle, Jéssica Andrade-da-Costa, Magdalena Leander, Helena Xavier-Ferreira, José Bessa, Carina Pereira, Rui M. Henrique, Fátima Carneiro, Mário Dinis-Ribeiro, Ricardo Marcos-Pinto, Margarida Lima, Bernd Lepenies, Harry Sokol, José C. Machado, Manuel Vilanova, Salomé S. Pinho
Supplementary Figures S1-S7
Funding
the Norte Portugal Regional Programme
Fundo Europeu de Desenvolvimento Regional
Fundação para a Ciência e a Tecnologia
European Research Council
FCT
History
ARTICLE ABSTRACT
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.