Siglec-10 (sialic acid-binding Ig-like lectin 10) is a member of the CD33-related Siglec family, a subgroup of type I transmembrane receptors characterized by extracellular immunoglobulin-like domains and cytoplasmic immunoreceptor-based tyrosine-based inhibitory motifs (ITIMs), which recruit the phosphatases SHP-1 and SHP-2 to attenuate activating immune signals (1). In humans, Siglec-10 is expressed in a variety of immune cell populations, including tumor-associated macrophages (TAMs), dendritic cells, natural killer (NK) cells, and subsets of activated T and B lymphocytes, with expression levels reportedly increasing significantly within the tumor microenvironment (2–4). The binding of Siglec-10 to its ligand CD24 triggers inhibitory signaling pathways that suppress the activation of T-cell receptors and NK cells, reduce cytokine production, and impair macrophage-mediated phagocytosis, thereby contributing to the establishment of a “don’t-eat-me” immune checkpoint (2).
Clinically, elevated Siglec-10 expression has been associated with poorer overall survival and independent prognostic significance, likely due to the accumulation of Siglec-10⁺ tumor-associated macrophages (TAMs) and their role in reshaping the tumor immune microenvironment (3-5).
