Epigenetic regulation of macrophage polarisation

There are two main macrophage subsets based on their cytokine pattern and phenotype: classical (or M1) and alternative (or M2). M1 macrophages promote anti-tumor immunity by supporting polarization of CD4 T-lymphocytes into anti-tumor Th1 and Th17. On the other hand, tumor associated macrophages (TAMs) that are close to M2 promote survival and proliferation of tumor cells. Evidence indicates that macrophage polarization is mediated by a transcriptional program that is influenced by epigenetic modifications. We investigated the effect of different epigenetic inhibitors on polarization of human macrophages. After isolation of human peripheral blood mononuclear cells, macrophages were polarized into M1 (using LPS+IFN-gamma) or M2 (with IL4) in presence or absence of inhibitors. Flow cytometry analyzes showed that epigenetic modulation affects CD206 expression on M2 macrophages, dextran-FITC phagocytosis and proliferation of allogeneic T-lymphocytes. Epigenetic inhibitors thus affect polarisation into M2 and may be useful to improve immunotherapy of cancer.