Surprisingly, arginine-depletion therapy paradoxically increases CD8+ T cells and pro-inflammatory TAMs in the TME, possibly due to the fact that T cells expressing argininosuccinate synthase 1 (ASS1) can synthesize arginine from citrulline and succinate, whereas ARG1+ TAMs and tumor cells are more dependent on extrinsic arginine (229–231). The gene discussed is CD8A; the disease is neoplasm.