ADI-PEG20 not only enhanced the cellular sensitivity of argininosuccinate synthetase 1-positive GBM to ionizing radiation by increasing NO production and hence the generation of cytotoxic peroxynitrites, but also promoted glioma-associated macrophage/microglial infiltration into the tumors, changing their classical anti-inflammatory (protumor) phenotype to a pro-inflammatory (anti-tumor) phenotype. This evidence concerns the gene ASS1 and central nervous system cancer.