Abstract
Sialic acids are sugars with a nine-carbon backbone, present on the surface of all cells in humans, including immune cells and their target cells, with various functions. Natural Killer (NK) cells are cells of the innate immune system, capable of killing virus-infected and tumor cells. Sialic acids can influence the interaction of NK cells with potential targets in several ways. Different NK cell receptors can bind sialic acids, leading to NK cell inhibition or activation. Moreover, NK cells have sialic acids on their surface, which can regulate receptor abundance and activity. This review is focused on how sialic acids on NK cells and their target cells are involved in NK cell function.
Highlights
As human Natural Killer (NK) cells express Siglec-7, which is known to bind α-2,8-linked sialic acids, it has been hypothesized that polysialic acid (polySia) on CD56/neural cell adhesion molecule (NCAM) might act as a masking ligand for Siglec-7
Sialic acids can be involved in NK cell function in two different ways
High levels of sialic acids can be beneficial for tumor cells, since binding of the activating receptors NKG2D to its ligands on tumor cells is reduced when they are sialylated
Summary
N-Acetylneuraminic acid (Neu5Ac) is the most common sialic acid in the human organism and the precursor for all other sialic acid derivatives. The key enzyme of the sialic acid biosynthesis is the bifunctional UDP-NAcetylglucosamine 2-epimerase/N-Acetylmannosamin kinase (GNE), catalyzing the first two reactions. The GNE is a bifunctional enzyme with the ability to catalyze two enzymatic reactions, the feedback inhibition is only affecting the UDP-GlcNAc epimerase activity [8]. Sialyltransferases themselves are a family of enzymes that catalyze sialylation, the attachment of a CMP-activated sialic acid scaffold onto glycoconjugates, through the loss of the nucleotide unit. The last two families are composed of the β-Galactoside α-2,6-(ST6Gal, EC 2.4.99.1) and the β-Galactoside α2,3-sialyltransferases (ST3Gal, EC 2.4.99.4), resulting in the formation of the corresponding glycosidic bond between the sialic acid (Neu5Ac) and galactose [14,15,16] (Figure 1). Cancer biomarkers like the sialyl Lewisa epitope (Neu5Acα2-3Galβ1-3(Fucα1-4) GlcNAc), the sialyl Lewisx motif, a structural isomer of Lewisa, and the sialyl-Tn epitope (Neu5Acα2-6GalNAc) have been reported to be used as targets for cancer immunotherapy in preclinical, as well as in clinical vaccine evaluation [26,27,28,29]
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