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

Data de publicação: Data Ahead of Print:

Autores da FMUP

  • Maria De Fátima Machado Henriques Carneiro

    Autor

  • Mário Jorge Dinis Ribeiro

    Autor

  • José Carlos Lemos Machado

    Autor

Participantes de fora da FMUP

  • Silva, MC
  • Fernandes, A
  • Oliveira, M
  • Resende, C
  • Correia, I.
  • de Freitas, JC
  • Lavelle, A
  • Andrade da Costa, J
  • Leander, M
  • Xavier Ferreira, H
  • Bessa, J
  • Pereira, C
  • Henrique, R.
  • Marcos Pinto, R
  • Lima, M
  • Lepenies, B
  • Sokol, H
  • Vilanova, M.
  • Pinho, SS

Unidades de investigação

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 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.

©2020 American Association for Cancer Research.

Dados da publicação

ISSN/ISSNe:
2326-6066, 2326-6074

Cancer Immunology Research  American Association for Cancer Research Inc.

Tipo:
Article
Páginas:
1407-1425
PubMed:
32933968
Link para outro recurso:
www.scopus.com

Citações Recebidas na Web of Science: 28

Citações Recebidas na Scopus: 38

Documentos

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Métricas

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Keywords

  • ANTITUMOR IMMUNITY; GLYCOSYLATION; BLOCKADE; TUMOR; STABILIZATION; INFLAMMATION; INNATE; ROLES; CELLS

Financiamento

European Research Council (ERC-2015-StG-680156-ZPR)
FCT (IF/00654/2013)
FCT (PTDC/BIM-MEC/2834/2014)
FCT (PTDC/MED-PAT/32462/2017)
Fundação para a Ciência e a Tecnologia (PTDC/BIM-MEC/2834/2014)
Fundação para a Ciência e a Tecnologia (PTDC/MED-PAT/32462/2017)
Fundação para a Ciência e a Tecnologia (SFRH/BD/136388/2018)
Fundacao para a Ciencia e a Tecnologia (SFRH/BD/136388/2018)
Fundo Europeu de Desenvolvimento Regional (FEDER) funds through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalization
i3S Scientific Platforms: Animal Facility and Translational Cytometry
Norte Portugal Regional Programme (NORTE 2020) under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund (NORTE-01-0145-FEDER-000029)
Portuguese Foundation for Science and Technology
Portuguese funds through the Portuguese Foundation for Science and Technology (POCI-01/0145-FEDER-016601/PTDC/DTP-PIC/0560/2014)
Portuguese funds through the Portuguese Foundation for Science and Technology (POCI-01-0145FEDER-028772)

Projetos associados

Effectiveness of endoscopic resection of colonic lesions > 20mm

Investigador Principal: Mário Jorge Dinis Ribeiro

Estudo Clínico Académico (Colonic lesions) . 2020

Gastric Cancer Morphological, Immunophenotypic and molecular heterogeneity

Investigador Principal: Maria de Fátima Machado Henriques Carneiro

Estudo Clínico Académico . 2020

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