{Reference Type}: Journal Article {Title}: Reversal of T-cell exhaustion: Mechanisms and synergistic approaches. {Author}: Hu Y;Zhang Y;Shi F;Yang R;Yan J;Han T;Guan L; {Journal}: Int Immunopharmacol {Volume}: 138 {Issue}: 0 {Year}: 2024 Sep 10 {Factor}: 5.714 {DOI}: 10.1016/j.intimp.2024.112571 {Abstract}: T cells suffer from long-term antigen stimulation and insufficient energy supply, leading to a decline in their effector functions, memory capabilities, and proliferative capacity, ultimately resulting in T cell exhaustion and an inability to perform normal immune functions in the tumor microenvironment. Therefore, exploring how to restore these exhausted T cells to a state with effector functions is of great significance. Exhausted T cells exhibit a spectrum of molecular alterations, such as heightened expression of inhibitory receptors, shifts in transcription factor profiles, and modifications across epigenetic, metabolic, and transcriptional landscapes. This review provides a comprehensive overview of various strategies to reverse T cell exhaustion, including immune checkpoint blockade, and explores the potential synergistic effects of combining multiple approaches to reverse T cell exhaustion. It offers new insights and methods for achieving more durable and effective reversal of T cell exhaustion.