BTN3A1 governs antitumor responses by coordinating αβ and γδ T cells
Kyle K. Payne, Jessica A. Mine, Subir Biswas, Ricardo A. Chaurio, Alfredo Perales‐Puchalt, Carmen M. Anadon, Tara Lee Costich, Carly M. Harro, Jennifer Walrath, Qianqian Ming, Evgenii N. Tcyganov, Andrea L. Buras, Kristen E. Rigolizzo, Gunjan Mandal, Jason Lajoie, Michael Ophir, Julia Tchou, Douglas C. Marchion, Vincent C. Luca, Piotr Bobrowicz, Brooke M. McLaughlin, Uğur Eskiocak, Michael M. Schmidt, Juan R. Cubillos‐Ruiz, Paulo C. Rodrı́guez, Dmitry I. Gabrilovich, José R. Conejo-García
Abstract
BTN3A1 governs antitumor responses T lymphocytes are immune cells that can be activated through their gamma delta (γδ) or alpha beta (αβ) receptors. Both T cell types are found in human cancers, but current immunotherapies do not harness their coordinated antitumor activity. Payne et al. found that BTN3A1 and BTN2A1, two members of the butyrophilin family of proteins, partner to activate the most abundant subset of γδ T cells in peripheral blood. Antibodies targeting BTN3A1 redirect γδ T cells to attack cancer cells while also increasing the activity of tumor-specific αβ T cells. Thus, the killing of established tumors by different T cell subsets can be achieved through BTN3A1 targeting and may provide new strategies for cancer immunotherapy. Science , this issue p. 942