One of the hallmarks of cancer is evading an immune response that should recognize emerging cancers as foreign and eliminate them. Immunotherapies are recent major breakthroughs in cancer treatment that reactivate the immune system to recognize and kill tumor cells. These novel treatments include immune checkpoint blockade where therapeutic antibodies remove a powerful break on the immune system to restore tumor killing, and cellular therapies where the patients’ own immune cells are engineered with superior tumor killing ability and then returned to the patient. Unfortunately, these new transformative treatments are only effective in a small subset of patients. If we could find the means to make immunotherapies more effective more broadly, it would transform cancer treatment and the lives of cancer patients.

One way to improve the anti-cancer immune response is by altering metabolism. Metabolic function and metabolite production can inhibit or promote activity of the immune system, but how they do so is poorly understood. It is the goal of the Ludwig Princeton Branch to understand how metabolism in tumor cells, the tumor microenvironment, and immune cells enables immune evasion. With that knowledge, we can identify the means to control metabolism through use of metabolic pathway inhibitors, metabolite supplementation, and dietary manipulation to restore the immune response to cancer and make immunotherapies more effective.