NOS2 and hepatocellular carcinoma: In this regard, the treatment with HEK 293 cell-derived EVs loaded with antisense oligonucleotides targeting STAT6 is highly effective at modifying the TME reprograming of M2-TAMs to the M1 phenotype in a model of colorectal carcinoma and a model of hepatoma, with increased expression of inducible nitric oxide synthase (iNOS), IL-1β, IL-12 and TNF-α [150].