Cancer-associated cell-surface glycans (TACAs)

Cancer-associated cell-surface glycans, also known as tumor-associated carbohydrate antigens (TACAs), are aberrant carbohydrate structures found on the surface of malignant cells due to altered glycosylation pathways. These changes often result in the truncation of O-glycans, increased branching of N-glycans, and hypersialylation, which distinguish tumor cells from their healthy counterparts (Pinho & Reis, 2015). Biologically, these glycans are pivotal in promoting tumor progression by facilitating cell-cell adhesion, enhancing metastatic potential through selectin interactions, and enabling immune evasion by engaging inhibitory receptors on immune cells (Munkley & Elliott, 2016). In the clinical setting, they serve as both diagnostic biomarkers (e.g., CA19-9, CA125) and therapeutic targets for monoclonal antibodies and vaccines (Zhou et al., 2023). While they offer high tumor specificity, challenges in targeting these glycans include their inherently low immunogenicity and the potential for off-target effects in tissues that share similar glycan motifs (NIH, 2023). Current research focuses on improving the affinity of anti-glycan therapeutics and developing glyco-immune checkpoint inhibitors to overcome the immunosuppressive tumor microenvironment.

Other names

Tumor-associated carbohydrate antigensAberrant tumor glycansCancer-specific glycansTumor-associated glycansCancer glycans

Therapeutic strategies targeting cancer-associated glycans include monoclonal antibodies that trigger antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against tumor cells (Zhou et al., 2023). Other mechanisms involve the use of glycomimetics to inhibit selectin-mediated cell adhesion and metastasis, or the development of carbohydrate-based vaccines designed to elicit a humoral immune response against tumor-specific glycan epitopes (Pinho & Reis, 2015). Additionally, emerging therapies aim to disrupt the sialic acid-Siglec signaling axis, which acts as a glyco-immune checkpoint to prevent immune evasion (Munkley & Elliott, 2016).