Cell-surface O-linked sialoglycans (O-sialoglycans)

Cell-surface O-linked sialoglycans are carbohydrate structures covalently attached to serine or threonine residues of proteins, characterized by terminal sialic acid residues (Varki A., Glycobiology, 2017). These glycans are essential components of the cell surface glycocalyx, playing pivotal roles in cell-cell recognition, adhesion, and immune modulation (Palleon Pharmaceuticals). In many cancers, an upregulation of sialyltransferases leads to hypersialylation, where an abundance of O-linked sialoglycans serves as a glyco-immune checkpoint by binding to inhibitory Siglec receptors on immune cells, such as NK cells and macrophages (Läubli H, et al., Curr Opin Oncol, 2020). This interaction effectively suppresses the immune response, allowing the tumor to evade detection and destruction (Gray MA, et al., Nat Chem Biol, 2020). Therapeutic strategies targeting these sialoglycans include the use of sialidases to strip the sialic acids from the cell surface or small molecules and antibodies that inhibit the enzymes responsible for their synthesis (Zhou JY, et al., Nat Rev Drug Discov, 2023).

Other names

Sialylated O-glycansO-linked sialic acidsMucin-type O-glycansSiglec ligandsTumor-associated sialoglycans

Enzymatic removal of terminal sialic acids (desialylation) from the cell surface to disrupt the immunosuppressive Siglec-sialoglycan axis and enhance anti-tumor immunity.