- berberine directly binds STAT3→ ↓ STAT3 phosphorylation and dimerization → ↓ IL-10 secretion by melanoma cells↑ IL-1β, TNF-α and IL-12 release from tumor-primed macrophages↓ IL-6 and TGF-β release from tumor-primed macrophages↓ IL-6-mediated STAT3 activation in macrophages- repolarized M2 macrophages to and M1 phenotype↑ MHC-II and CD40 expression on macrophages↓ FOXP3 and GATA-3↑ T-bet↑ IFN-γ release from CD4+ T cellsLeading to: ↓ melanoma tumor volume in vivo. Here, TNF is linked to melanoma.