CTLA4 and B-cell chronic lymphocytic leukemia: Although studies have documented a higher number of CD8+ T cells in CLL patients compared with age-matched healthy individuals, these cells often express exhaustion markers (i.e., programmed death cell protein 1[PD-1], cytotoxic T-lymphocyte associated protein 4 [CTLA-4], and lymphocyte-activation gene 3 [LAG-3]) and demonstrate reduced cytotoxic activity, which is perpetuated by improper immune synapse formation (29–31).