Immunometabolism is an emerging field that researchers are investigating to advance cellular therapy against cancer. Tumor tissues are heterogeneous, and the tumor microenvironment (TME) is characterized by hypoxia, acidosis, nutrient deprivation and immunosuppression. Tumor cells and immune cells compete for metabolites in the nutrient deplete TME, and the balance is often skewed in favor of the tumor cells, resulting in altered anticancer immunity. Therefore, metabolic reprogramming of immune effector cells may enhance their fitness, effector function and anti-tumor potency. Understanding the metabolic competition between tumor cells and immune cells for access to limited nutrients in the complex TME could help in developing novel strategies to enhance the efficacy of adoptive cellular therapy. This session will focus on recent discoveries in the field of immunometabolism and will highlight the exciting opportunities to metabolically reprogram immune cells to enhance their fitness and optimize their therapeutic efficacy.

Dr. May Daher will discuss various engineering and gene editing strategies to enhance the metabolic fitness of immune effector cells in the context of adoptive cell therapy.  Enhancing the metabolic fitness of immune cells will lead to more potent effector function against tumors, improved persistence, memory formation and decreased functional exhaustion. Some of the strategies we will highlight are metabolic manipulation during manufacturing, the choice of CAR costimulatory domain, CRISPR gene editing of checkpoint molecules, and pharmacologic approaches.

Dr. Greg Delgoffe will discuss the basic concepts in immunometabolism, with a specific focus on metabolic control of T cell differentiation and function. We will also introduce potential strategies to metabolically prepare T cells for therapeutic treatment of cancer, including both pharmacologic and genetic approaches.