CTLA4 and neoplasm: The rationale for selecting the components of the CRI regimen is based on different and complementary mechanisms of their action: local RT induces tumor cell death and tumor antigen release thus serving as in situ vaccine (19); srIL-2 induces T/NK cell activation, proliferation and survival (18); anti-CTLA-4 induces T cell activation via checkpoint blockade (1–3) and Treg depletion via antibody-dependent cell-mediated cytotoxicity through an Fc effector mechanism (17, 28, 29); and IL-12 induces T/NK cell activation and IFN-γ release leading to macrophage activation (22).