Sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9)

Sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) is a cell surface inhibitory receptor belonging to the immunoglobulin superfamily and the Siglec subgroup of lectins. It is primarily expressed on human immune cells including neutrophils, monocytes, and subsets of lymphocytes. Siglec-9 binds to sialic acid–containing glycans (sialoglycans) present on host and some pathogenic cells, acting as a glycoimmune checkpoint that dampens immune cell activation and prevents self-reactivity. The receptor contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in its cytosolic domain, which, upon ligand engagement, recruit SHP phosphatases to inhibit intracellular signaling pathways and suppress inflammation. Siglec-9's broad ligand recognition allows it to serve as a key regulator of immune homeostasis and a target for cancer immunotherapy, as many tumors exploit the Siglec-9 pathway to evade immune detection. Targeting Siglec-9 with engineered glycans or other agents is a focus of current immuno-oncology research due to its role in immune suppression and its tractability as a cell surface receptor[1][3][4][6].

Other names

Siglec-9CD329SIGLEC9sialic acid-binding Ig-like lectin 9

Inhibition of immune cell activation via ITIM (immunoreceptor tyrosine-based inhibitory motif) phosphorylation leading to SHP1/SHP2 recruitment and downstream signaling[3][4]. Potential competitive inhibition of Siglec-9 binding with exogenous high-affinity glycan ligands or sialidase-mediated desialylation of target cells[1][3].