CTLA4 and cancer: Its expression increases with the activation of T cells.368 In 1992, the United States FDA (Food and Drug Administration) approved high-dose IL-2 therapy for clinical use, which enables expansion of cultured lymphocytes.369 Soon thereafter, PD-1 (programmed death ligand 1) was discovered, also in 1992.370 Then, in 1994, Allison et al. reported cancer rejection following anti-CTLA-4 blockade.371,372 Since then, numerous advances have been achieved.