Targeting the αvβ5 Integrin Modifies the TGF-β-Rich Tumor Microenvironment of Pancreatic Cancer

Here, we demonstrated that the αv integrin- and neuropilin-1 (NRP-1)-dual targeting iRGD peptide reverses some of these TME features by inhibiting transforming growth factor-β (TGF-β) activation in the tumor, a process mediated by the αvβ5 integrin.

In addition to PDAC epithelial cells and fibroblasts, regulatory T cells (Tregs) in PDAC tumors also expressed the αvβ5 integrin and NRP-1. The αvβ5+ Tregs potently inhibited T cell proliferation, and systemic iRGD therapy not only depleted αvβ5+ Tregs from PDAC tumors but also reduced their αvβ5- counterparts. Mechanistically, iRGD inhibited the activation of TGF-β mediated by the αvβ5-rich TME, thereby depriving Tregs of the cytokine essential for their development and maintenance.