The hypothesis that TIGIT may represent a critical collaborator of the PD-1/PD-L1 engagement in order to limit the activity of chronically stimulated CD8+ T cells is supported by the observation that co-blockade of TIGIT and PD-1 is essential to restore the anti-tumor functional activity of effector CD8+ T cells within the highly immunosuppressive TME. Here, TIGIT is linked to neoplasm.