Sialic acid-binding immunoglobulin-type lectin receptor (Siglec)

Siglecs are a family of immunoglobulin-like transmembrane receptors that recognize sialic acid-containing glycans found on host and pathogen surfaces. Mostly expressed on immune cells, they regulate cell signaling, typically through immunoreceptor tyrosine-based inhibitory motifs (ITIMs) leading to suppression of activation, though some can signal through immunoreceptor tyrosine-based activating motifs (ITAMs). The Siglec family is divided into two groups: a conserved subgroup (e.g., Siglec-1/sialoadhesin, Siglec-2/CD22, Siglec-4/MAG, Siglec-15) and a more rapidly evolving group (CD33-related Siglecs, e.g., Siglec-3, Siglec-5–11, -14, -16). Siglecs play critical roles in immune regulation, including self/non-self discrimination, regulation of inflammation, and immune tolerance. They are implicated in numerous diseases, especially cancer, where tumors exploit Siglec pathways to evade immune surveillance

Other names

SiglecSialic acid-binding lectinI-type lectinsialoadhesin (for Siglec-1)CD22 (for Siglec-2)CD33 (for Siglec-3)Myelin-associated glycoprotein/MAG (for Siglec-4)CD33-related Siglecs

Antibody–dependent targeting (e.g., antibody-drug conjugates against leukemia/lymphoma via CD33) Immune modulation (enhance or inhibit signaling in immune cells) Blockade or activation of Siglec function to modulate immune evasion in cancer or autoimmunity