The Roles of Siglec7 and Siglec9 on Natural Killer Cells in Virus Infection and Tumour Progression

Abstract

The function of natural killer (NK) cells, defending against virus infection and tumour progression, is regulated by multiple activating and inhibiting receptors expressed on NK cells, among which sialic acid-bind immunoglobulin-like lectins (Siglecs) act as a vital inhibitory group. Previous studies have shown that Siglec7 and Siglec9 are expressed on NK cells, which negatively regulate the function of NK cells and modulate the immune response through the interaction of sialic acid-containing ligands. Siglec7 and Siglec9 are very similar in distribution, gene encoding, protein sequences, ligand affinity, and functions in regulating the immune system against virus and cancers, but differences still exist between them. In this review, we aim to discuss the similarities and differences between Siglec7 and Siglec9 and analyze their functions in virus infection and tumour progression in order to develop better anti-viral and anti-tumor immunotherapy in the future.

Coronaviruses: Is Sialic Acid a Gate to the Eye of Cytokine Storm? From the Entry to the Effects

“…Varki and Angata hypothesize that expression of sialic acids by the envelope of CoV can affect Siglec receptors biology in the hosts and thereby regulate the reactivity of innate immune cells [ 102 ]. The inhibitory receptors, such as Siglec-5, -7 and -9, are implicated in molecular mimicry mechanism that allow several pathogens to avoid immunesurveillance as shown in the hepatitis B virus (HBV) infections [ 106 , 107 ]. In the context of Siglec-mediated immune regulation, the clinical differences in the CoVs infections can be interpreted by the variety of human phenotypes.…”

Harnessing NK cells for cancer immunotherapy: immune checkpoint receptors and chimeric antigen receptors

“…Sialic acids, cognate ligands of Siglecs are 9-carbon-backbone monosaccharides, which are the glycan residues of glycoproteins and glycolipids. The cytoplasmic domains of Siglec7 and Siglec9 contain an ITIM and an ITIM-like motif ( 92 ). Siglec7 and Siglec9 share structural similarity and functionality but have different roles in virus infection and tumors.…”

“…Hypersialylated tumor cells can bind to Siglec9, and Siglec9 + NK cells express higher levels of KIRs and LIR-1. Siglec7 interacts with gangliosides, while Siglec9 interacts with mucins ( 92 ). Importantly, the desialylation of tumor cells by neuraminidases enhanced NK cytotoxicity and cytokine production ( 94 ), thereby implying novel therapeutic approaches.…”

From Classical to Unconventional: The Immune Receptors Facilitating Platelet Responses to Infection and Inflammation

“…Though the stimulation of Siglec 7 by ganglioside, its ligand, does not lead to platelet aggregation, its cross linking has been shown to induce platelet apoptosis [ 175 ]. As Siglec 7 has been shown to have inhibitory effects in natural killer cells [ 176 ], it is possible that platelet apoptosis is a way to negatively regulate the inflammatory responses mediated by platelets. Furthermore, the sialic acid groups from capsule of Group B Streptococci , have also been shown to inhibit platelet activation by engaging Siglec 9 on the platelet surface [ 40 ].…”