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

Sialic acid-binding Ig-like lectin 9 (Siglec-9), and its murine ortholog Siglec-E, are inhibitory receptors belonging to the CD33-related Siglec family. Primarily expressed on myeloid cells such as neutrophils, monocytes, and macrophages, these receptors play a crucial role in maintaining immune homeostasis by recognizing self-associated molecular patterns (SAMPs) in the form of sialoglycans (UniProt Q9Y336). Upon binding to sialic acids, Siglec-9/E recruits tyrosine phosphatases SHP-1 and SHP-2 via its intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs), thereby dampening activating signals from receptors like TLRs or Fc receptors (Duan & Paulson, 2020, Annu Rev Immunol). In oncology, the sialic acid-Siglec axis is recognized as a potent glyco-immune checkpoint; tumors often hypersialylate their surface to engage Siglec-9/E on tumor-associated macrophages and neutrophils, effectively evading immune surveillance (Läubli & Varki, 2020, Curr Opin Struct Biol). Therapeutic strategies currently under investigation include the use of sialidase-Fc fusion proteins (e.g., E-602) to strip sialic acids from the tumor surface and monoclonal antibodies to block the Siglec-9 receptor directly (Palleon Pharmaceuticals, 2024). Beyond cancer, Siglec-E/9 is implicated in controlling excessive inflammation in conditions like sepsis and acute lung injury, where its loss leads to hyper-inflammatory phenotypes (PubMed 25108027).

Other names

Siglec-ESialic acid-binding Ig-like lectin ECD170Siglec-9Sialic acid-binding Ig-like lectin 9

Sialidase-mediated desialylation of tumor cell surface ligands to prevent inhibitory signaling; monoclonal antibody-mediated blockade of the Siglec-9 receptor to prevent engagement with sialoglycan ligands.