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

Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of cell-surface transmembrane receptors that specifically recognize sialic acid-containing glycans (sialoglycans) [1, 2]. In the context of oncology, tumor cells frequently exhibit hypersialylation, a process where they overexpress sialic acids on their surface glycoproteins and glycolipids to create a "glyco-immune checkpoint" [6, 9]. These sialoglycans act as ligands that bind to inhibitory Siglecs (such as Siglec-7, Siglec-9, and Siglec-15) expressed on immune cells or, in the case of Siglec-15, on the tumor cells themselves [10, 13]. This interaction triggers inhibitory signaling through immunoreceptor tyrosine-based inhibitory motifs (ITIMs), effectively dampening the activity of natural killer (NK) cells, macrophages, and T cells to facilitate immune evasion [2, 6]. Therapeutic strategies targeting this axis include monoclonal antibodies that block Siglec receptors (e.g., NC-318), antibody-drug conjugates (e.g., gemtuzumab ozogamicin), and sialidases (e.g., E-602) that strip sialic acids from the tumor surface to restore immune activation [1, 5, 15].

Other names

Sialic acid receptorSiglec familyCD33-related SiglecsI-type lectinsSialoglycan-binding receptorsSialic acid-binding immunoglobulin-type lectins

Drugs targeting this axis primarily function through immune checkpoint blockade to restore anti-tumor immunity, antibody-drug conjugate (ADC) mediated delivery of cytotoxic payloads to Siglec-expressing cells, or enzymatic desialylation of the tumor surface to remove immunosuppressive sialoglycans [1, 5, 15].