Manipulation of metabolic pathways to promote stem-like and memory T cell phenotypes for immunotherapy

Utilizing the immune system's capacity to recognize and kill tumor cells has revolutionized cancer therapy in recent decades. Phenotypic study of antitumor T cells supports the principle that superior tumor control is achieved by cells with more long-lived memory or stem-like properties as compared to terminally differentiated effector cells. In this Mini-Review, we explore recent advances in profiling the different metabolic programs that both generate and define subsets of memory T cells. We additionally discuss new experimental approaches that aim to maximize the durability and sustained antitumor response associated with memory T cells within the unique immunosuppressive conditions of the tumor microenvironment, such as engineered attempts to overcome hypoxia-induced changes in mitochondrial function, the inhibitory effects of tumor metabolites, and exploitation of more recently-defined metabolic pathways controlling T cell memory fate such as glycogen metabolism.

Automated summary

Utilizing the immune system's capacity to recognize and kill tumor cells has revolutionized cancer therapy. Recent studies on antitumor T cells suggest that long-lived memory or stem-like cells have superior tumor control compared to terminally differentiated effector cells. This Mini-Review explores the profiling of metabolic programs that generate and define subsets of memory T cells. It also discusses experimental approaches to enhance the durability and sustained antitumor response of memory T cells in the immunosuppressive tumor microenvironment, including overcoming hypoxia-induced changes in mitochondrial function, inhibitory effects of tumor metabolites, and regulation of T cell memory fate through glycogen metabolism.