An anti-PD-1/L1 lead-in period before MAPK inhibitor combination optimizes response duration through the promotion of pro-inflammatory macrophage polarization and clonal expansion of IFN-γ high and CD8 + cytotoxic and proliferative T cells in murine models of melanoma driven by BRAF V600, NRAS, or Nf1 mutations, as well as colorectal and pancreatic carcinoma driven by KRAS G12C [73]. This evidence concerns the gene NRAS and melanoma.