Glycoscience in Advancing PD-1/PD-L1-Axis-Targeted Tumor Immunotherapy

Area of Science:

• Immunology
• Oncology
• Glycoscience

Background:

• Immune checkpoint blockade (ICB) therapy using anti-PD-1/PD-L1 antibodies has revolutionized cancer treatment.
• However, limitations include low response rates, immune-related adverse effects, and resistance.
• Aberrant glycosylation is increasingly recognized as a key factor in cancer progression and immune evasion.

Purpose of the Study:

• To review the role of glycosylation in the PD-1/PD-L1 axis.
• To highlight advances in glycoscience (glycotherapy) for improving ICB efficacy.
• To explore personalized medicine strategies targeting cancer glycosylation.

Main Methods:

• Literature review of studies on glycosylation, PD-1/PD-L1, and immunotherapy.
• Analysis of recent achievements in glycotherapy and glycoengineering.
• Discussion of therapeutic strategies targeting cancer-specific glycosylation patterns.

Main Results:

• PD-1 and PD-L1 proteins are highly glycosylated, influencing their interactions and antibody binding.
• Glycoengineered antibodies show improved binding affinity to PD-1/PD-L1.
• Inhibitors of core fucosylation and sialylation, and antibody-sialidase conjugates demonstrate therapeutic potential.

Conclusions:

• Targeting aberrant cancer glycosylation offers a promising avenue for precision medicine.
• Glycotherapy represents a potent strategy to enhance the effectiveness of PD-1/PD-L1 blockade therapies.
• Advances in glycoscience are crucial for overcoming current limitations in cancer immunotherapy.