In cancer, TIM3+ PD-1+ CD8+ TILs are associated with the most dysfunctional or terminal stage of CD8+-T cell exhaustion, whereas single positive TIM3- PD-1+ CD8+ TILs exhibit a weaker exhaustion/dysfunctional stage and double negative TIM3- PD-1- CD8+ TILs possess good effector function [25,52,106]. The gene discussed is PDCD1; the disease is cancer.