Siglec family protein member (Siglec)

Siglecs (Sialic acid-binding immunoglobulin-like lectins) are a family of cell surface receptors predominantly expressed on immune cells. Structurally, they are type I transmembrane proteins within the immunoglobulin superfamily, featuring an N-terminal V-set Ig domain responsible for binding sugars containing sialic acid. Most Siglecs contain cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that negatively regulate immune cell activation, although some associate with activating adaptors such as DAP12 to transduce stimulatory signals. Siglecs play vital roles in immune cell signaling, self/non-self discrimination, phagocytosis regulation, and modulation of inflammation. Altered Siglec signaling is implicated in cancer (tumor immune evasion and immunosuppression), infection, inflammatory diseases, and bone disorders. Multiple Siglec members are currently under investigation as targets for immunotherapy, especially for tumors that evade immune detection by exploiting the sialic acid–Siglec signaling axis[1][2][3][4][5][6]. Note: For drug targeting or advanced research, always specify the exact member of the Siglec family (e.g., Siglec-7, Siglec-15), as they differ significantly in structure, function, and tissue distribution.

Other names

Sialic acid-binding immunoglobulin-like lectinsCD22 (Siglec-2)CD33 (Siglec-3)Sialoadhesin (Siglec-1)MAG (Siglec-4, myelin-associated glycoprotein)

Inhibition of immunosuppressive Siglec signaling to enhance immune activation (immune checkpoint blockade) Antibody-dependent cell-mediated cytotoxicity (ADCC) Targeted delivery of cytotoxic agents (antibody–drug conjugates) Blocking sialic acid binding to disrupt tumor–immune cell interactions