NOS2 and neoplasm: The conversionof tumor-associated macrophages (TAMs) from an immunosuppressive M2-polarizedphenotype to an anti-tumor M1-polarized phenotype is one of the majorimmunotherapeutic strategies for reprogramming the immunosuppressiveTME.26 Addition of esterase to the culturemedium followed by 24 h of incubation resulted in morphological changeof the M2-state toward the round and flattened M1-state, a decreasein Arg1 and Mrc1, and an increase in IL-12 and Nos2 expression (Figures 2h and S11).