Sialic acid-binding Ig-like lectin 10 (Siglec-10) (Siglec-10)

Sialic acid-binding Ig-like lectin 10 (Siglec-10) is an inhibitory receptor predominantly expressed on the surface of various immune cells, including B cells, monocytes, and tumor-associated macrophages (UniProt Q96LC7). It belongs to the CD33-related Siglec family and contains intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that mediate suppressive signaling upon ligand binding (Barkal et al., Nature 2019). Siglec-10 has emerged as a critical immune checkpoint in oncology, where its interaction with CD24 on tumor cells serves as a "don't eat me" signal, preventing macrophages from phagocytosing malignant cells (Barkal et al., Nature 2019). Beyond its role in cancer immune evasion, Siglec-10 is involved in regulating the innate immune response to danger-associated molecular patterns (DAMPs) and maintaining peripheral tolerance (Chen et al., Science 2009). Therapeutic interventions targeting the Siglec-10/CD24 axis, such as the fusion protein CD24Fc (MK-7110), are being investigated for their ability to dampen hyper-inflammatory states or enhance anti-tumor immunity (ClinicalTrials.gov NCT04317040).

Other names

SLG2Siglec-like protein 2PRO940CD330

Blockade of the CD24/Siglec-10 inhibitory axis to enhance macrophage phagocytosis of tumor cells (Barkal et al., Nature 2019) or agonism/stabilization of the pathway to suppress inflammatory responses to DAMPs (Chen et al., Science 2009).