The Immune Consequences of Lactate in the Tumor Microenvironment

Abstract

The tumor microenvironment consists of complex and dynamic networks of cytokines, growth factors, and metabolic products. These contribute to significant alterations in tissue architecture, cell growth, immune cell phenotype, and function. Increased glycolytic flux is commonly observed in solid tumors and is associated with significant changes in metabolites, generating high levels of lactate. While elevated glycolytic flux is a characteristic metabolic adaption of tumor cells, glycolysis is also a key metabolic program utilized by a variety of inflammatory immune cells. As such lactate and the pH changes associated with lactate transport affect not only tumor cells but also immune cells. Here we provide an overview of lactate metabolic pathways and the effects lactate has on tumor growth and immune cell function. This knowledge provides opportunities for synergistic therapeutic approaches that combine metabolic drugs, which limit tumor growth and support immune cell function, together with immunotherapies to enhance tumor eradication.