In CLL, T-cell exhaustion is mediated by upregulation of co-inhibitory signals such as programmed death-1 (PD1), lymphocyte activation gene-3 (LAG-3), cytotoxic T-lymphocyte-associated protein-4 (CTLA4), and T-cell immunoglobin-3 (TIM-3). This evidence concerns the gene CTLA4 and B-cell chronic lymphocytic leukemia.