In conclusion, immunomodulatory changes in the context of BRAF/MEK inhibitor resistance are characterized by decreased NK cell activation, M2 macrophage polarization driven by VEGF-A and tumor-derived factors, impaired T cell function, reduced dendritic cell infiltration (cDC1, cDC2, and CD40+CCR7+ subsets), Treg cell accumulation, and melanoma antigen loss due to MAPK reactivation and tumor dedifferentiation. This evidence concerns the gene CD40 and neoplasm.