CTLA4 and neoplasm: Thus, combining IL-2 therapy with CTLA-4 blockade, which enables costimulation in tumor-specific T cells,27 would be most effective when checkpoint inhibition is implemented first, allowing for more effective CTLA-4 blockade as well as more robust IL-2-mediated activation due to increased CD25 expression together with elimination of PD-1 and CTLA-4 inhibitory signals on tumor-specific effector T cells.