During the process of in vitro expansion and repetitive stimulation, along with the high concentrations of inhibitory cytokines in the tumor microenvironment, CAR-T cells develop an exhausted phenotype (upregulation of PD-1, LAG3, TIM3, and TIGIT and decreased secretion of IL-2, TNF-α, and IFN-γ). This evidence concerns the gene TNF and neoplasm.