The Immunoreceptor TIGIT Regulates Antitumor and Antiviral CD8+ T Cell Effector Function
Menée sur des lignées cellulaires et à l'aide de modèles murins, cette étude met en évidence le rôle joué par le récepteur TIGIT dans l'inhibition de l'activité antitumorale du système immunitaire
Tumors constitute highly suppressive microenvironments in which infiltrating T cells are “exhausted” by inhibitory receptors such as PD-1. Here we identify TIGIT as a coinhibitory receptor that critically limits antitumor and other CD8+ T cell-dependent chronic immune responses. TIGIT is highly expressed on human and murine tumor-infiltrating T cells, and, in models of both cancer and chronic viral infection, antibody coblockade of TIGIT and PD-L1 synergistically and specifically enhanced CD8+ T cell effector function, resulting in significant tumor and viral clearance, respectively. This effect was abrogated by blockade of TIGIT’s complementary costimulatory receptor, CD226, whose dimerization is disrupted upon direct interaction with TIGIT in cis. These results define a key role for TIGIT in inhibiting chronic CD8+ T cell-dependent responses.
Cancer Cell , résumé, 2013