NOS2 and neoplasm: Activated MDSC produce elevated levels of nitric oxide (NO) via inducible nitric oxide synthase (iNOS) and upregulate the expression of arginase-1 (ARG-1), both leading to cell cycle arrest in T cells via depletion of the amino acid l-arginine from the tumor microenvironment (41, 42) and to T cell anergy induced by the downregulation of T cell receptor (TCR) ζ-chain expression (16, 43).