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

Mariana C Silva1,2, Ângela Fernandes1, Maria Oliveira1

  • 1Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal.

Cancer Immunology Research
|September 16, 2020
PubMed

Insights

Colorectal cancer cells use branched N-glycans to evade immune detection by inhibiting interferon-gamma (IFNγ). Removing these glycans exposes mannose, enhancing immune cell recognition and triggering an antitumor response.

Area of Science:

  • Oncology
  • Immunology
  • Glycobiology

Background:

  • Tumor growth involves significant alterations in the cellular glycome, including aberrant expression of complex branched N-glycans.
  • The precise role of these protumoral N-glycans in immune evasion and their potential for enhancing antitumor immunity are not fully understood.

Purpose of the Study:

  • To investigate the role of branched N-glycans in colorectal cancer immune evasion.
  • To determine if removing these glycans can enhance immune recognition and stimulate an antitumor response.

Main Methods:

  • Analysis of N-glycan expression in colorectal cancer cells.
  • Investigating the impact of N-glycan removal on immune cell interactions and cytokine production, specifically interferon-gamma (IFNγ).
  • Assessing the effect of deglycosylation on immune recognition by dendritic cell-specific intercellular adhesion molecule-3-grabbing non-tanner (DC-SIGN) expressing immune cells.

Main Results:

  • Branched N-glycans on colorectal cancer cells facilitate immune evasion by inhibiting IFNγ signaling, creating an immunosuppressive environment.
  • Removal of these branched N-glycans unmasked immunogenic mannose glycans.
  • Deglycosylation potentiated immune recognition by DC-SIGN+ immune cells, leading to a robust antitumor immune response.

Conclusions:

  • A novel glycoimmune checkpoint in colorectal cancer has been identified, mediated by branched N-glycans.
  • Deglycosylation represents a promising therapeutic strategy to enhance immune recognition and improve cancer immunotherapy efficacy.

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