Direct strategies include (i) depletion of metabolites essential for T-cell proliferation such as L-arginine, which is necessary for T-cell fitness and anti-tumor activity, through the expression of arginase-1 (ARG1), (ii) production of reactive oxygen species (ROS), (iii) expression of immune checkpoint ligands such as programmed cell death ligands (PDL1 and PDL2), cytotoxic T-lymphocyte-associated protein 4 (CTLA4) (B7-1 and B7-2) and B7-H4, and (iv) producing anti-inflammatory cytokines such as IL-10 and TGF-β (209, 234). The gene discussed is CTLA4; the disease is neoplasm.