Understanding the Crosstalk Between Epigenetics and Immunometabolism to Combat Cancer.

The interaction between metabolic and epigenetic events shapes metabolic adaptations of cancer cells and also helps rewire the proliferation and activity of surrounding immune cells in the tumor microenvironment (TME). Recent studies indicate that the TME imposes metabolic constraints on immune cells, inducing them to attain a tolerogenic state, incompetent of mounting effective tumor eradication. Owing to extensive mutations acquired over repeated cell divisions, tumor cells selectively accumulate metabolites that regulate the activity of key epigenetic enzymes to mediate activation/suppression of genes associated with T-cell function and macrophage polarization. Further, multiple modulators connecting epigenetic and metabolic pathways help dictate the preferential induction of cytokines and expression of lineage-specifying genes associated with immunosuppressive T-cell differentiation.In this chapter, we attempt to discuss the mechanisms underpinning the metabolic and epigenetic interplay in immune cells of the TME and how modulating these events can boost the application of existing anticancer immunotherapy.