Sialic acid-containing cell surface glycans

Sialic acid-containing cell surface glycans, often referred to as sialoglycans, are terminal sugar modifications on glycoproteins and glycolipids that are significantly upregulated on the surface of many tumor cells, a phenomenon known as hypersialylation. These glycans serve as a critical glyco-immune checkpoint by binding to inhibitory Siglec (sialic acid-binding immunoglobulin-like lectin) receptors on immune cells, such as NK cells, macrophages, and T cells, thereby suppressing the anti-tumor immune response. Beyond immune evasion, hypersialylation promotes tumor progression by enhancing cell survival, facilitating metastasis through altered cell adhesion, and contributing to chemoresistance. Therapeutic strategies targeting this axis include enzymatic desialylation using sialidase fusion proteins, monoclonal antibodies against specific sialylated antigens, and inhibitors of sialyltransferase enzymes. These approaches aim to strip the protective glycan coat from tumor cells to restore immune recognition and enhance the efficacy of other immunotherapies.

Other names

Tumor-associated sialoglycansHypersialylated glycansTumor sialoglycansSialic acid-Siglec axis ligandsTumor-associated carbohydrate antigens (TACAs)

Desialylation (enzymatic removal of sialic acids), Siglec blockade (preventing inhibitory signaling), Inhibition of sialyltransferase (blocking glycan synthesis), and Antibody-dependent cellular cytotoxicity (ADCC).