Fig. 5

T cell exhaustion causes PD-1 blockade therapy resistance. PD-1 blockade promotes the secretion of cytokines, including IFN-γ and TNF, leading to the expression of ligands of inhibitory receptors, including LAG3 and TIM-3, in tumor cells and activation-induced cell death (AICD). Additionally, PD-1 blockade can attenuate the expression or activity of a series of genes and promote T cell exhaustion. Furthermore, after PD-1 blockade, tumor cells show high oxygen consumption, which causes hypoxia in the tumor microenvironment, promoting the exhaustion of T cells. Moreover, NSE1 activity in TILs is inhibited, which affects glycolysis and leads to T cell depletion