PD-1 and LAG-3 double knockout CD8+ T cells exhibit higher TCR diversity, stronger cytotoxicity (increased expression of GZMB and PRF1), and IFN-γ dependent anti-tumor effects (53, 54), while the combination of PD-1 with TIM-3 or TIGIT blockade is still in the exploratory stage. This evidence concerns the gene HAVCR2 and neoplasm.