They activate the antitumor cytotoxicity of T cells and natural killer cells.123,124 Engineered Salmonella producing IL-2 and IL-18 was shown to inhibit tumor growth in animal experiments.125,126 Targeting programmed cell death protein-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) by immune-checkpoint inhibitors is a revolutionary cancer immunotherapy strategy but has side effects such as fatigue, skin rashes, and endocrine disorders.127,128 Increasing l-arginine levels in tumor tissue can activate the response of immune-checkpoint inhibitors. This evidence concerns the gene CTLA4 and cancer.