Recent data have revealed that CTLA-4, the first “immune checkpoint” to enter the clinic as cancer immunotherapeutic agent, is more expressed by Tregs than effector T cells in peripheral lymphoid organs and in blood and even more at the tumor site, and that anti-CTLA-4 antibodies may work through antibody-dependent cell-mediated cytotoxicity and Treg depletion (6–9); this finding proves the key role of Tregs as a non-redundant and even dominant immune checkpoint in the tumor microenvironment. The gene discussed is CTLA4; the disease is neoplasm.