Metabolic control of antitumor immunity

The metabolism of cancer cells adapts to meet an increased need for the energy, biosynthesis, and antioxidants required for proliferation, tumor growth, and metastasis (1). Yet, whether this metabolic reprogramming affects the recognition and elimination of cancer cells by immune cells has not been well investigated. On page 1316 of this issue, Mangalhara et al. (2) report a connection between a cancer cell's mitochondrial metabolism and its ability to evoke an immune response in a mouse model of melanoma. Specific perturbations of the mitochondrial electron transport chain increased succinate production in cancer cells. Succinate accumulation caused epigenetic rearrangements, which induced the expression of genes involved in antigen presentation. This promoted the detection of tumor cells by surveilling T cells-tumor immunogenicity. The identification of a mechanism by which mitochondrial metabolites shape tumor immunogenicity has potential for developing anticancer therapies.