CD8A and neoplasm: By analyzing CD57, a marker expressed at terminal differentiation stage, we observed more than 40% CD8 + T cells expressed CD57 in conventional CAR-T cells after co-culture with tumor cells, while about 20% CD8 + T cells were CD57 positive in IL-7-secreting CAR T cells co-cultured with tumor cells (Fig. 3G), demonstrating that conventional CAR signaling over activated CD8 + T cells and most likely induced downregulation of metabolic activity due to leading to terminal differentiation state.