MNK2 governs the macrophage antiinflammatory phenotype

Abstract

Significance The tumor-associated macrophage (TAM) phenotype is continuously modulated during tumor progression to facilitate immune escape. Yet, how gene expression programs control TAM phenotypes during this process is largely unknown. Here we show that, during acquisition of a protumor phenotype, gene expression in TAMs is predominantly modulated via selective changes in mRNA translation rather than changes in mRNA abundance. Detailed studies pinpointed augmented activity of MNK2, which phosphorylates eIF4E and thereby modulates mRNA translation, as required for the antiinflammatory macrophage phenotype. Accordingly, suppression of MNK2 reeducated antiinflammatory macrophages toward a proinflammatory phenotype with the ability to activate CD8 + T cells.