Our study demonstrates that SATB1 overexpression mitigates CAR-T cell exhaustion and improves anti-tumor efficacy, potentially not only through mechanisms involving broadly suppression of inhibitory receptors (PD-1, CTLA-4, TIM3 and LAG-3) (Figs. S5 and S6) but also promotion of CD45RA− CD62L+ T cell subsets and CCR7+ T cell subsets (Figs. 3G–J and S3A–S3D) and enhanced resistance to TGF-β-mediated immunosuppression (Fig. S4) in the HCC microenvironment. Here, LAG3 is linked to hepatocellular carcinoma.