Cell-surface sialoglycan (Sialoglycan)

Cell-surface sialoglycans are carbohydrate structures terminating in sialic acid residues that are frequently overexpressed on the surface of cancer cells, a phenomenon known as hypersialylation (Gray et al., Nature, 2020). These glycans function as ligands for Siglecs (Sialic acid-binding immunoglobulin-type lectins), which are inhibitory receptors expressed on various immune cells, including natural killer (NK) cells, macrophages, and T cells (Zhou et al., Nature Reviews Drug Discovery, 2023). The interaction between tumor sialoglycans and Siglecs constitutes a glyco-immune checkpoint that suppresses immune cell activation and promotes tumor evasion from the host immune system (Stanczak et al., JCI, 2018). Therapeutic interventions targeting this axis include sialidases, such as E-602, which enzymatically remove sialic acids to strip the tumor's protective coating and enhance anti-tumor immunity (Palleon Pharmaceuticals, 2024). Additionally, sialyltransferase inhibitors and Siglec-blocking antibodies are being developed to disrupt this immunosuppressive signaling pathway. By targeting the sialic acid-Siglec axis, these therapies aim to restore potent immune responses across a broad range of solid tumors.

Other names

Sialic acid-containing glycansTumor-associated sialoglycansSiglec ligandsHypersialylated glycansSialylated glycans

Enzymatic desialylation of the cell surface to remove terminal sialic acids, thereby disrupting the interaction with inhibitory Siglec receptors and restoring immune cell activation against tumor cells.