In contrast, during chronic infections and cancer, chronically stimulated antigen-specific T cells progressively decrease in quantity and function as they enter a state of hyporesponsivness called “T cell exhaustion”, characterized by the loss of cytokine production and proliferative potential, development of metabolic dysfunction and increased expression of inhibitory receptors (IRs), including PD-1, Tim-3 and CTLA-4. This evidence concerns the gene CTLA4 and cancer.