Figure 2. Mechanism of action of ipilimumab.

T cell activation requires stimulation through both the TCR and CD28. Binding of B7 family member proteins to CTLA-4 inhibits T cell function. Notably, CTLA-4 expression increases in parallel with TCR stimulation, thereby serving as a break on T cell responses. Anti–CTLA-4 antibodies such as ipilimumab block CTLA-4 binding to B7 proteins and prevent inhibition of T cell function. Reproduced from ref. 54.