The (Sialyl) Tn antigen: Contributions to immunosuppression in gastrointestinal cancers

Area of Science:

• Biochemistry and Molecular Biology
• Immunology
• Oncology

Background:

• Cellular signaling pathways are critical for homeostasis but are often dysregulated in cancer.
• O-glycosylation, a post-translational modification, generates glycoproteins, including Tn and Sialyl Tn (STn) antigens, implicated in pancreatic and gastrointestinal cancers.
• The tumor microenvironment (TME), comprising immune cells and other components, significantly influences tumor progression and metastasis.

Purpose of the Study:

• To review the role of Tn and STn antigens in cancer progression.
• To elucidate how Tn and STn antigens modulate the tumor immune microenvironment (TIME).
• To explore potential therapeutic strategies targeting the interaction between Tn/STn antigens and the TIME.

Main Methods:

• Literature review of studies on O-glycosylation, Tn/STn antigens, and the tumor microenvironment in gastrointestinal cancers.
• Analysis of signaling pathways involved in the interaction between tumor antigens and immune cells.
• Synthesis of current understanding of immunosuppressive mechanisms mediated by Tn/STn antigens.

Main Results:

• Tn and STn antigens, resulting from incomplete O-glycosylation, are associated with disease progression in gastrointestinal cancers.
• Expression of Tn/STn antigens on tumors alters the function of immune cells within the TIME, suppressing anti-tumor activity.
• These antigens mediate immunosuppression through various cell-intrinsic and extrinsic signaling pathways.

Conclusions:

• The interaction between Tn/STn antigens and the TIME is a key factor in the progression of gastrointestinal cancers.
• Targeting these interactions offers a promising avenue for developing novel cancer therapies.
• Understanding these mechanisms can help overcome immunosuppression and sensitize tumors to existing treatments.