Tumor-associated sialoglycan

Tumor-associated sialoglycans are cell-surface molecules, including glycoproteins and glycolipids, that are modified with terminal sialic acid residues. In many cancers, an overabundance of these sialic acids, known as hypersialylation, serves as a potent mechanism of immune evasion by creating a glyco-immune checkpoint (Nature Reviews Cancer, 2020). These sialic acids act as ligands for Siglec (Sialic acid-binding immunoglobulin-type lectin) receptors on various immune cells, such as natural killer (NK) cells, neutrophils, and T cells, delivering inhibitory signals that suppress the anti-tumor immune response (Frontiers in Immunology, 2021). Therapeutic strategies targeting these sialoglycans include the use of sialidases, such as E-602, to strip the tumor's protective coating, thereby sensitizing the tumor to immune attack (Palleon Pharmaceuticals). Additionally, small molecule inhibitors of sialyltransferases and antibodies targeting specific sialoglycans like GD2 are used to disrupt this axis and improve outcomes in oncology (Journal of Biological Chemistry, 2019). By removing or blocking these sugars, the immune system can more effectively recognize and destroy malignant cells.

Other names

Cell-surface sialic acid-containing receptorTumor sialoglycanHypersialylated glycoconjugateSialic acid-containing glycanSiglec ligand

Enzymatic removal of terminal sialic acids (desialylation) to disrupt the Sialic acid-Siglec immune checkpoint axis or direct targeting of specific sialoglycans to induce antibody-dependent cellular cytotoxicity (ADCC).