CTLA4 and neoplasm: The discovery that cytotoxic T-lymphocyte-associated protein 4 (CTLA4)- and programmed cell death protein 1 (PD-1)-dependent mechanisms provide the basis for the physiologic peripheral immunological tolerance supported the rationale that blocking the inhibitory signals mediated by CTLA-4 or PD-1 would promote activation of T cells that can recognize tumor antigens and induce anti-tumor responses.