This study investigated the efficacy of CAR-T cells targeting tmTNF-α against breast cancer. The results demonstrated that tmTNF-α-CAR-T cells effectively killed tmTNF-α-positive tumor cells and inhibited tumor growth. Furthermore, blocking the PD-1/PD-L1 pathway synergized with and enhanced the anti-tumor efficacy of tmTNF-α CAR-T cell therapy. The gene discussed is CD274; the disease is breast cancer.