Despite the studies which provide insight into the intrinsic mechanism of LAG-3/CD8 interaction remain scarce, it is newly reported that there may exist two additional LAG-3 ligands in the tumor microenvironment to help regulate CD8+ T cells-galectin-3 and Liver sinusoidal endothelial cell lectin (LSECtin), which could effectively abolish anti-tumor immunity of CD8+ T cells via LAG-3 [58, 59]. The gene discussed is CD8A; the disease is neoplasm.