CD4 and neoplasm: Since MAPKi promote increased tumor infiltration and IFN-γ secretion by both CD4+ and CD8+ T cells in BRAFV600E+ melanoma animal models [30, 31], it is feasible that TNFR2 upregulation on patient melanomas results from a negative feedback loop mediated by MAPKi-enhanced Th1-type tumor-specific T cell responses.