Taken together, our data demonstrate the ability of MEK inhibition, via selumetinib, to reduce immune suppression in the TME through multiple cellular and molecular mechanisms, and although further studies are required to confirm our observations, suggest that up-regulation of the Cox-2/Arg1 pathway within the tumor could represent an adaptive resistance mechanism to anti-CTLA-4 therapy, which is alleviated through combination with MEK inhibition. The gene discussed is CTLA4; the disease is neoplasm.