Glycans as Immune Checkpoints: Removal of Branched N-glycans Enhances Immune Recognition Preventing Cancer Progression
Mariana Silva
(1, 2)
,
Ângela Fernandes
(1)
,
Maria Oliveira
(1)
,
Carlos Resende
(1)
,
Alexandra Correia
(1, 2)
,
Julio De-Freitas-Junior
(3)
,
Aonghus Lavelle
(4)
,
Jéssica Andrade-Da-Costa
(3)
,
Magdalena Leander
(5)
,
Helena Xavier-Ferreira
(1, 2)
,
José Bessa
(1)
,
Carina Pereira
(6, 7)
,
Rui Henrique
(7)
,
Fátima Carneiro
(1, 8)
,
Mário Dinis-Ribeiro
(6, 7)
,
Ricardo Marcos-Pinto
(2, 8, 9)
,
Margarida Lima
(5)
,
Bernd Lepenies
(10, 11)
,
Harry Sokol
(4)
,
José Machado
(1, 8)
,
Manuel Vilanova
(1, 2)
,
Salomé Pinho
(1, 8)
1
I3S -
Instituto de Investigação e Inovação em Saúde
2 ICBAS - Instituto de Ciências Biomédicas de Abel Salazar
3 INCA - Instituto Nacional de Câncer [Rio de Janeiro]
4 Pathologies biliaires, fibrose et cancer du foie [CRSA]
5 Centro Hospitalar do Porto
6 CINTESIS - Center of Research in Health Technologies and Information Systems
7 IPO Porto - Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto
8 Universidade do Porto = University of Porto
9 Centre for Research in Health Technologies and Information Systems (CINTESIS)
10 Max Planck Institute of Colloids and Interfaces
11 University of Veterinary Medicine [Hannover]
2 ICBAS - Instituto de Ciências Biomédicas de Abel Salazar
3 INCA - Instituto Nacional de Câncer [Rio de Janeiro]
4 Pathologies biliaires, fibrose et cancer du foie [CRSA]
5 Centro Hospitalar do Porto
6 CINTESIS - Center of Research in Health Technologies and Information Systems
7 IPO Porto - Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto
8 Universidade do Porto = University of Porto
9 Centre for Research in Health Technologies and Information Systems (CINTESIS)
10 Max Planck Institute of Colloids and Interfaces
11 University of Veterinary Medicine [Hannover]
Mariana Silva
- Fonction : co premier-auteur
Harry Sokol
- Fonction : Auteur
- PersonId : 801170
- IdHAL : harry-sokol
- ORCID : 0000-0002-2914-1822
- IdRef : 128516313
Salomé Pinho
Connectez-vous pour contacter l'auteur
- Fonction : Auteur correspondant
- PersonId : 1109964
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Résumé
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 IFN gamma. 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.
