In studies on tumor-inoculated mice, it was shown that CAR-T cells deficient in both TOX and TOX2, or with triple KO of NR4A1, NR4A2, and NR4A3, had a greater anti-cancer activity and improved animal survival; therefore, targeting the TOX/NR4A axis may reduce the depletion of CAR-T cells in TME [124,125]. The gene discussed is TOX; the disease is cancer.