Integrating metabolic engineering and immunotherapy

Abstract Immune cells hold enormous potential to specifically target and kill cancer cells. Yet, tumors have evolved to inactivate T cells and evade the immune system. T cell cytotoxicity is regulated by various stimulatory and inhibitory signals in order to balance inflammation with immune tolerance. Immunotherapy has found these to represent unique targets to potentiate T cells in a tumor context. Besides immune signals, cellular metabolism represents an additional and crucial layer of T cell activity. Notably, nutrients can maintain T cell cytotoxicity within the metabolic hurdles of their microenvironment. Therefore, metabolic therapy represents a complementary approach to conventional immunotherapy strategies to improve patient outcomes. In this review, we discuss how immune signals and cellular metabolism integrate and ultimately regulate the ability of T cells to operate in the tumor microenvironment. Moreover, we review key studies showing the benefit of targeting together those signals to effectively dismantle tumor growth.