Abstract
Advances in radiation delivery technologies and immunotherapy have improved effective cancer treatments and long-term outcomes. Experimental and clinical trials have demonstrated the benefit of a combination of radiation therapy and immunotherapy for tumor eradication. Despite precise radiation dose delivery that is achievable by particle therapy and benefits from reactivating the antitumor immune response, resistance to both therapeutic strategies is frequently observed in patients. Understanding the biological origins of such resistance will create new opportunities for improved cancer treatment. Cancer metabolism and especially a high rate of aerobic glycolysis leading to overproduction and release of lactate is one such biological process favoring tumor progression and treatment resistance. Because of their known protumor effects, aerobic glycolysis and lactate production are potential targets for increased efficacy of radiation alone or in combination with immunotherapy. In the following review, we present an overview of the interplay of cancer cell lactate metabolism with the tumor microenvironment and immune cells. We discuss how a deeper understanding and careful modulation of lactate metabolism and radiation therapy might exploit this interplay for improved therapeutic outcome.