Considering the fact that CTLA-4 and PD-1 regulate different stages of the immune response (CTLA-4 regulates the early stages of T-cell activation, while PD-1 is expressed after the T-cells are activated) and that they exert their actions at different sites (draining lymph nodes for CTLA-1 and tumor microenvironment for PD-1 and its ligands), it is understandable that their effects and adverse reactions are different (18–20). The gene discussed is PDCD1; the disease is neoplasm.