NOS2 and neoplasm: M1 macrophages are activated by IFN-γ, lipopolysaccharide (LPS), and granulocyte macrophage-colony stimulating factor (GM-CSF) and then secrete IFN-γ, IL-6, IL-12, tumor necrosis factor-alpha (TNF-α), reactive oxygen species (ROS), and nitric oxide synthase (NOS), exhibiting pro-inflammatory features such as promoting the destruction of tumor cells, recruiting tumor-killing leukocytes, or directly phagocytosing tumor cells (44).