Mixed-Up Sugars: Glycosyltransferase Cross-Reactivity in Cancerous Tissues and Their Therapeutic Targeting

Area of Science:

• Glycobiology
• Cancer Biology
• Immunology

Background:

• Glycan expression undergoes significant alterations in cancer.
• Key changes include altered histo-blood group antigens, cryptic antigens, genetically incompatible glycans, and neoglycans.

Purpose of the Study:

• This review focuses on genetically incompatible A/B/Forssman antigen (FORS1) expression in cancer.
• It explores molecular mechanisms driving these aberrant glycan expressions.
• The potential of these glycans as immunotherapeutic targets is discussed.

Main Methods:

• Review of existing literature on cancer glycan changes.
• Analysis of molecular mechanisms underlying incompatible glycan synthesis.
• Discussion of immunotherapeutic strategies.

Main Results:

• Genetically incompatible glycans, including A, B, and FORS1 antigens, emerge in cancer.
• Mechanisms include mutations in glycosyltransferases, altered codon reading frames, and modified acceptor specificities.
• These aberrant glycans can be potential targets for cancer immunotherapy.

Conclusions:

• Aberrant expression of genetically incompatible glycans in cancer presents unique immunogenic properties.
• Understanding these mechanisms is crucial for developing novel cancer immunotherapies.
• Targeting these specific glycans may harness natural immunity for therapeutic benefit.