Regulatory T cells (Tregs) play a critical role in preventing autoimmunity but can be co-opted by cancer cells to block immune surveillance of tumors. One immunosuppressive mechanism of Tregs is the contact-dependent release of transforming growth factor–β1 (TGF-β1), which is bound to the Treg surface by the protein GARP. Cuende et al. reported that GARP also contributes to the release of active TGF-β1 and that monoclonal antibodies targeting GARP blocked release of TGF-β1, thereby blocking immunosuppressive activity. In a xenogeneic mouse model of graft-versus-host disease (GVHD), coadministration of Tregs with the xenografted cells delays the onset of GVHD and injection with the monoclonal antibodies targeting GARP blocked this immunosuppressive effect. Thus, blocking GARP, either alone or in combination with other checkpoint inhibitors, could add to our arsenal for cancer immunotherapy.
J. Cuende, S. Liénart, O. Dedobbeleer, B. van der Woning, G. De Boeck, J. Stockis, C. Huygens, D. Colau, J. Somja, P. Delvenne, M. Hannon, F. Baron, L. Dumoutier, J.-C. Renauld, H. De Haard, M. Saunders, P. G. Coulie, S. Lucas, Monoclonal antibodies against GARP/TGF-β1 complexes inhibit the immunosuppressive activity of human regulatory T cells in vivo. Sci. Transl. Med. 7, 284ra56 (2015). [Abstract]