Sialic acid-binding Ig-like lectin 7 (SIGLEC7)

Sialic acid-binding Ig-like lectin 7 (SIGLEC7), also known as CD328 or p75/AIRM1, is a type I transmembrane protein and a member of the CD33-related Siglec family. It is predominantly expressed on natural killer (NK) cells, monocytes, and subsets of T cells, where it functions as an inhibitory receptor. SIGLEC7 contains an extracellular V-set Ig domain that binds to sialic acid-containing glycans, such as α2,8-linked disialic acids, and an intracellular immunoreceptor tyrosine-based inhibitory motif (ITIM). Upon ligand binding, the ITIM is phosphorylated and recruits phosphatases like SHP-1 and SHP-2, which dampen activating signals and suppress immune cell effector functions. In the context of oncology, many tumors overexpress sialylated ligands to exploit this pathway, creating a "glyco-immune checkpoint" that allows them to evade NK cell-mediated lysis and T-cell responses. High expression of SIGLEC7 or its ligands is often associated with poor prognosis in various cancers, including colorectal, breast, and prostate cancer. Consequently, SIGLEC7 is a target of interest for cancer immunotherapy, with therapeutic strategies including antagonistic monoclonal antibodies and sialidase-fusion proteins designed to disrupt the Siglec-sialic acid axis and restore anti-tumor immunity.

Other names

CD328p75AIRM1Adhesion inhibitory receptor molecule 1D-siglecQA79 membrane protein

Antagonism of the inhibitory signaling pathway by blocking the interaction between Siglec-7 and its sialylated ligands, or by enzymatic removal of sialic acid ligands, thereby restoring immune cell activation and anti-tumor cytotoxicity.