In the reverse case, when the switch from PD-1 therapy to CTLA-4 therapy occurred, new effector cells had to be generated to catch up with the density present when CTLA-4 therapy was administered first; however, since PD-1 therapy proved to be more potent initially in reducing the tumor size and therefore, the number of antigens (tumor burden) that is required for priming, CTLA-4 therapy promoted a greater enhancement of response from less tumor burden than was feasible with PD-1 therapy at first. Here, CTLA4 is linked to neoplasm.