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

The Glycoprotein A repetitions predominant–Transforming growth factor beta-1 complex (GARP:TGF-β1 complex) is a cell surface complex where the membrane protein GARP (also known as LRRC32) binds and presents latent TGF-β1 on cells such as regulatory T cells, platelets, macrophages, and certain tumor cells[4][5][3]. GARP acts as a surface anchor and chaperone, holding TGF-β1 in its inactive (latent) form until it is activated by interaction with integrins (notably αVβ6 and αVβ8); once activated, TGF-β1 is released, mediating potent immunosuppressive and tissue-regulatory effects[2][7][4]. The complex is a critical checkpoint in immune regulation: regulatory T cells rely on GARP:TGF-β1 to exert local immunosuppressive effects, especially within the tumor microenvironment[4][5]. Dysregulation of this axis can contribute to immune escape in cancer, making the complex a rational therapeutic target for immuno-oncology. Therapeutic interventions aim to block the activation or presentation of TGF-β1 by GARP, often via monoclonal antibodies, to boost anti-tumor immunity[2][4][1]. The structural and mechanistic understanding of this complex is a focus for the development of novel immunomodulatory drugs and biomarkers.

Other names

GARP–latent TGF-β1 complexGARP–TGF-beta-1 complexGARP–TGF-beta complexLRRC32–TGF-β1 complex

Antibody blockade of the GARP:TGF-β1 complex to inhibit activation/release of TGF-β1, thereby reducing immunosuppression and enhancing anti-tumor immunity[2][4]