It is well established that chronic infection and many cancers cause T-cell exhaustion, characterized by progressive loss of T-cell effector functions and memory properties, up-regulation of inhibitory receptors such as PD-1, lymphocyte activation gene 3 (LAG3), T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), and cytotoxic T lymphocyte antigen 4 (CTLA-4) on T cells [128]. This evidence concerns the gene HAVCR2 and cancer.