Although not as disputed as the PD-1/PD-L1 system, the lymphocyte-activation gene (LAG-3), member of the immunoglobulin superfamily and expressed on the surface of activated regulatory CD4+ and CD8+ T cells, B cells and NKT cells have also been shown to contribute to tumor immunesuppression, as Tregs from LAG-3(−/−) mice present reduced regulatory activity [104]. This evidence concerns the gene CD8A and neoplasm.