Roles of glycosylation at the cancer cell surface: opportunities for large scale glycoproteomics

Area of Science:

• Biochemistry
• Immunology
• Oncology

Background:

• Cell surface glycosylation plays crucial roles in cellular functions.
• Dysregulated glycosylation in cancer is linked to impaired signaling, metastasis, and immune evasion.
• Specific glycosyltransferases (B3GNT3, FUT8, B3GNT2) are associated with reduced anti-tumor immune responses.

Purpose of the Study:

• To provide an overview of altered cell surface glycosylation in cancer.
• To highlight examples of receptors with aberrant glycosylation affecting cancer progression and immune response.
• To emphasize the need for unbiased methods to interrogate cell surface glycosylation.

Main Methods:

• Review of literature on cell surface glycosylation changes in cancer.
• Discussion of specific examples of aberrant glycosylation on key receptors.
• Exploration of the potential of glycoproteomics for large-scale profiling.

Main Results:

• Cancer cells exhibit broad changes in surface glycosylation.
• Aberrant glycosylation of immune checkpoint inhibitors, growth-promoting, and growth-arresting receptors impacts cancer.
• Glycosyltransferases like B3GNT3, FUT8, and B3GNT2 are implicated in immune evasion.

Conclusions:

• The field of glycoproteomics is advanced enough for large-scale profiling of cell surface glycopeptides.
• Such profiling can lead to the discovery of new actionable cancer targets.
• Understanding aberrant glycosylation is critical for developing novel cancer immunotherapies.