Glycoprotein A repetitions predominant (GARP)–latent transforming growth factor beta 1 (TGF-β1) complex (GARP–latent TGF-β1 complex)

The Glycoprotein A repetitions predominant (GARP)–latent transforming growth factor beta 1 (TGF-β1) complex is a cell-surface molecular assembly consisting of the transmembrane protein GARP (also known as LRRC32) and the inactive, latent form of TGF-β1 (Metelli et al., 2018). GARP serves as a critical docking receptor that anchors latent TGF-β1 to the surface of regulatory T cells (Tregs) and platelets, facilitating its subsequent activation by integrins such as αVβ6 and αVβ8 (Stockis et al., 2017). This complex is a primary regulator of immune tolerance, as the release of active TGF-β1 suppresses effector T cell responses and promotes an immunosuppressive tumor microenvironment (de Streel et al., 2020). In various cancers, including breast, lung, and colon carcinomas, the complex is overexpressed, contributing to immune evasion and disease progression (AbbVie Science, 2024). Therapeutic strategies involve monoclonal antibodies, such as livmoniplimab (ABBV-151), that specifically bind the complex to block the release of active TGF-β1, thereby reinvigorating the anti-tumor immune response (NIH, 2024). This targeted approach offers a potential advantage over systemic TGF-β inhibition by minimizing off-target effects on the pleiotropic functions of TGF-β in normal tissues (Metelli et al., 2018). Clinical trials are currently investigating these inhibitors in combination with PD-1/PD-L1 blockade to overcome resistance in solid tumors (AbbVie Science, 2024). Beyond oncology, the complex is also a potential target in autoimmune and inflammatory diseases where modulating Treg function could restore immune homeostasis (Patsnap, 2024).

Other names

LRRC32–latent TGF-β1 complexGARP–LTGF-β1 complexGARP–proTGF-β1 complexGlycoprotein A repetitions predominant–latent TGF-beta 1 complex

Monoclonal antibodies bind to the GARP–latent TGF-β1 complex to prevent the release of active TGF-β1, thereby inhibiting TGF-β1-mediated immunosuppression.