Cell-surface sialic acid (Sia) (Sia)

Cell-surface sialic acids are a family of nine-carbon acidic monosaccharides typically found at the terminal positions of N-linked and O-linked glycans on glycoproteins and glycolipids (Varki A, 2008). They are essential components of the "sialome," playing pivotal roles in cell-cell recognition, molecular masking, and the regulation of the innate and adaptive immune systems (Cohen M, et al., 2010). By interacting with Sialic acid-binding immunoglobulin-type lectins (Siglecs), these residues function as "self-associated molecular patterns" (SAMPs) that suppress overactive immune responses (Läubli H, et al., 2020). In oncology, many tumors exhibit hypersialylation, which facilitates immune evasion by engaging inhibitory Siglecs on natural killer (NK) cells and macrophages (Pearce OM, et al., 2016). Furthermore, sialic acids serve as critical attachment points for numerous pathogens, most notably the influenza virus, which uses hemagglutinin to bind these residues for host cell entry (Skehel JJ, et al., 2000). Therapeutic interventions include neuraminidase inhibitors that prevent viral spread and emerging glyco-immune checkpoint inhibitors designed to disrupt the sialic acid-Siglec axis in the tumor microenvironment (Zhou X, et al., 2020).

Other names

N-acetylneuraminic acidNeu5AcSialic acid residuesTerminal sialic acidN-glycolylneuraminic acid

Inhibition of viral neuraminidase to prevent the cleavage of terminal sialic acid residues from host cell surfaces, thereby trapping viral progeny; blockade of sialic acid-binding receptors like P-selectin to prevent cell adhesion; and disruption of the sialic acid-Siglec immune checkpoint to enhance anti-tumor immunity (Varki A, 2008; Zhou X, et al., 2020).