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). The gene discussed is HAVCR2; the disease is neoplasm.