How metabolism bridles cytotoxic CD8+T cells through epigenetic modifications

In the direct competition for metabolic resources between cancer cells and tumorinfiltrating CD8+ T cells, the latter are bound to lose out. These effector lymphocytes are therefore rendered exhausted or dysfunctional. Emerging insights into the mechanisms of T cell unresponsiveness in the tumor microenvironment (TME) point towards epigenetic mechanisms as crucial regulatory factors. In this review, we discuss the effects of characteristic components of the TME, i. e. glucose/amino acid dearth with elevated levels of reactive oxygen species (ROS), on DNA methylation and histone modifications in CD8+ T cells. We then take a closer look at the translational potential of epigenetic interventions that aim to improve current immunotherapeutic strategies, including the adoptive transfer of T cell receptor (TCR) or chimeric antigen receptor (CAR) engineered T cells.

Automated summary

In the tumor microenvironment, CD8+ T cells face competition for metabolic resources from cancer cells, leading to impaired epigenetic mechanisms and functional limitations. This study discusses the impact of glucose/amino acid deficiency and elevated ROS levels in the TME on DNA methylation and histone modifications in CD8+ T cells, as well as the translational potential of epigenetic interventions to enhance current immunotherapeutic strategies.