Anti-4-1BB monoclonal antibodies (which could act in the periphery to increase T cell frequencies or in the tumor microenvironment to restore function of anergic cells) combined with anti-PD-L1 also appear synergistic [59,129], as is combined elimination of LAG-3 and PD-1 function [130] or anti-Tim-3 plus anti-PD-L1 [131]. The gene discussed is CD274; the disease is neoplasm.