Common lymphatic and endothelial vascular endothelial receptor 1 (CLEVER-1)

Common lymphatic and endothelial vascular endothelial receptor 1 (CLEVER-1), also known as Stabilin-1, is a large type I transmembrane scavenger receptor and adhesion molecule (UniProt P78324). It is predominantly expressed on lymphatic endothelial cells, sinusoidal endothelial cells of the liver and spleen, and pro-tumoral M2-polarized macrophages (Palani et al., 2016). CLEVER-1 facilitates the endocytosis of various ligands, such as SPARC and acetylated LDL, and regulates the trafficking of lymphocytes and monocytes (Karikoski et al., 2014). In cancer, CLEVER-1 acts as an immune checkpoint by maintaining an immunosuppressive environment that prevents T-cell mediated anti-tumor responses (Viitala et al., 2019). Therapeutic agents like bexmarilimab target CLEVER-1 to reprogram macrophages from an immunosuppressive M2 phenotype to a pro-inflammatory M1 phenotype (Faron Pharmaceuticals, 2024). This phenotypic switch enhances the recruitment and activation of cytotoxic T cells within the tumor microenvironment. Beyond oncology, CLEVER-1 is involved in chronic inflammation and fibrosis due to its role in tissue remodeling and waste clearance (Kzhyshkowska et al., 2006).

Other names

Stabilin-1STAB1FEEL-1Fasciclin, EGF-like, laminin-type EGF-like, and link domain-containing scavenger receptor-1MS-1 antigen

Monoclonal antibody antagonist that blocks the immunosuppressive function of CLEVER-1 on tumor-associated macrophages, promoting a phenotypic switch from M2 (pro-tumoral) to M1 (anti-tumoral) to enhance T-cell mediated immune responses (Faron Pharmaceuticals, 2024).