NOS2 and neoplasm: Therefore, the spatial distribution of M1 and M2 TAMs provides a more accurate reflection of disease prognosis than merely assessing the presence of different TAM phenotypes in the TME.467 Furthermore, TAMs secrete various cytokines that promote the development of corresponding tumor phenotypes,468 such as direct secretion of growth factors that stimulate tumor growth.469 For instance, M1 macrophages upregulate inducible nitric oxide synthase (iNOS), which metabolizes L-arginine to L-citrulline and nitric oxide, creating a microenvironment unfavorable for tumor progression.