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

Sialic acid-binding Ig-like lectin 7 (Siglec-7), also known as CD328 or p75/AIRM1, is a key inhibitory checkpoint receptor predominantly expressed on human Natural Killer (NK) cells and monocytes (UniProt Q9Y286). It belongs to the CD33-related Siglec family and functions as a self-recognition molecule by binding to specific sialic acid-containing glycans (sialoglycans), particularly alpha-2,8-linked disialic acids, on the cell surface (Glycopedia). In many cancers, tumor cells undergo hypersialylation, overexpressing Siglec-7 ligands to engage the receptor and trigger inhibitory signaling through its cytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIMs) (Frontiers in Immunology, 2019). This recruitment of SHP-1 and SHP-2 phosphatases dampens NK cell-mediated cytotoxicity and cytokine production, facilitating tumor immune evasion (NIH, 2024). Therapeutic strategies targeting the Siglec-7 axis include blocking monoclonal antibodies and sialidase-fusion proteins, such as E-602, which enzymatically remove sialic acids to restore immune activity (Palleon Pharmaceuticals). Beyond oncology, Siglec-7 is implicated in viral infections like HIV-1 and may serve as a biomarker for disease progression or therapeutic response (NIH, 2025).

Other names

CD328p75/AIRM1SIGLEC7QA79p75AIRM1Adhesion inhibitory receptor molecule 1D-siglec

Sialidase-mediated desialylation of cell surface glycans to prevent Siglec-7 binding and block ITIM-mediated inhibitory signaling (Palleon Pharmaceuticals).