Integrin alpha-V beta-8 (αvβ8) (αvβ8)

Integrin alpha-V beta-8 (αvβ8) is a heterodimeric transmembrane receptor composed of the alpha-V (ITGAV) and beta-8 (ITGB8) subunits [1, 5]. Unlike most integrins that primarily mediate cell adhesion to the extracellular matrix, αvβ8 functions as a critical and specialized activator of latent transforming growth factor-beta (specifically TGF-β1 and TGF-β3) [1, 11]. It achieves this by binding to the RGD motif within the latency-associated peptide (LAP) of TGF-β, facilitating the release of the active cytokine into the local environment [12, 16]. This process is essential for maintaining immune homeostasis and regulating tissue development, particularly in the brain and gastrointestinal tract [1, 15]. In disease states, αvβ8 is often overexpressed in various cancers and fibrotic tissues [1, 12]. In the tumor microenvironment, αvβ8-mediated TGF-β activation promotes immunosuppression by inhibiting the activity of cytotoxic T cells, thereby allowing tumors to evade the immune system [4, 16]. In fibrotic conditions, such as idiopathic pulmonary fibrosis, it drives the activation of myofibroblasts and excessive collagen production [7, 17]. Consequently, αvβ8 has become a high-priority therapeutic target, with several small molecules and monoclonal antibodies, such as bexotegrast and ADWA-11, in development to selectively inhibit TGF-β activation at disease sites while avoiding the toxicities associated with systemic TGF-β blockade [2, 11, 16].

Other names

Integrin αvβ8ITGAV-ITGB8alphaVbeta8Integrin alpha V beta 8ITGAV/ITGB8

Inhibition of latent TGF-beta activation by blocking the binding of the integrin to the RGD motif of the Latency Associated Peptide (LAP).