Therapeutic targeting of amino acids in tumors and the tumor microenvironment. The most common amino acid–depletion strategies include depletion of Asn with asparaginase (ASNase), Arg with arginase (ARGase), or Arg deiminase (ADI), Glu with glutaminase (GLS) inhibitors, and Cys/cysteine (CSSC) with cysteinase. Stromal cells or adipocytes produce Asn and Glu, supporting tumor metabolism. ARGase secretion by tumor cells (which depletes extracellular Arg) and/or tumor consumption of Gln may deprive immune cells of these nutrients, and metabolic inhibitors of ARGase or GLNase reverse immune suppression. GSH, glutathione; NK, natural killer; ROS, reactive oxygen species; TCA, the citric acid.