%0 Journal Article
%T Reversal of T-cell exhaustion: Mechanisms and synergistic approaches.
%A Hu Y
%A Zhang Y
%A Shi F
%A Yang R
%A Yan J
%A Han T
%A Guan L
%J Int Immunopharmacol
%V 138
%N 0
%D 2024 Sep 10
%M 38941674
%F 5.714
%R 10.1016/j.intimp.2024.112571
%X 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.