Improving Immune Checkpoint Therapy in the Tumor Microenvironment by Targeting T Cell Metabolism.

Abstract

To meet the increased nutrient requirements associated with rapid cellular proliferation, tumor cells undergo metabolic reprogramming, characterized by a substantial increase in the production of energy and precursor molecules necessary for biosynthetic processes. Similarly, T cells experience metabolic reprogramming to support their proliferation and immunological functions, leading to metabolic competition with tumor cells within the tumor microenvironment (TME). This metabolic competition adversely affects T cell activation, proliferation, and immune function, primarily due to the limited availability of glucose, lipids, and amino acids. Furthermore, cytokines and immune checkpoints significantly impact T cell-mediated immunoreactivity. Modulating the metabolism of tumor cells and T cell-mediated immune evasion within the TME is of paramount importance. Notably, the metabolism of small-molecule target agents has garnered considerable attention in the context of the TME. This study aimed to examine the influence of various microenvironmental factors on T cell metabolism and explore corresponding innovative therapeutic approaches, thereby offering a comprehensive array of potential clinical strategies for cancer prevention and treatment.