Integrins αvβ8 and αvβ1

Class

Oral dual integrin inhibitor

Pathway

Integrin-mediated activation of latent TGF-β; tumor immune evasion

Integrins αvβ8 and αvβ1 are cell-surface adhesion receptors that, beyond anchoring cells to the extracellular matrix, perform a specialized signaling role: they activate latent transforming growth factor-beta (TGF-β). TGF-β is secreted in an inactive form bound to a latency-associated peptide, and it must be released before it can signal. These integrins recognize a specific motif on that latent complex and physically or enzymatically trigger its activation. Once freed, TGF-β exerts broad effects on tissue remodeling and immune regulation, and within tumors it is a major driver of immune evasion — suppressing cytotoxic T-cell activity, promoting regulatory T cells, and creating a fibrotic barrier that excludes immune cells from tumor tissue. αvβ8 is prominently expressed on tumor and immune cells, while αvβ1 is more associated with stromal fibroblasts; targeting both aims to interrupt TGF-β activation across the several cell types that sustain it within the tumor microenvironment, rather than addressing only one source. An oral small-molecule dual inhibitor of these integrins is being explored as a strategy to restore anti-tumor immune activity across cancers where TGF-β-driven immune exclusion limits treatment efficacy.