Preclinical studies demonstrated that when CD40 agonists were combined with CSF1R inhibitors in murine models of melanoma, TAMs secreted pro-inflammatory cytokines, such as IL-1b and IL-27, and reduced their expression of MMP9, suggesting an effective, albeit temporary, reprogramming.96,101 In addition to this, an enhanced T cell response against melanoma was reported, which was macrophage dependent.96,101 These data suggest that the reprogramming of TAMs has the potential to play an important role in promoting an anticancer TME, which in turn enables improved T cell effector function. This evidence concerns the gene CD40 and melanoma.