AUTHOR=Claiborne Michael D. TITLE=Manipulation of metabolic pathways to promote stem-like and memory T cell phenotypes for immunotherapy JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1061411 DOI=10.3389/fimmu.2022.1061411 ISSN=1664-3224 ABSTRACT=

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.