In this setting, cis interaction of PD-1 and PD-L1 on tumor cells or APC rendered T cells more activated.[27] However, the possibility of cis interaction between T cell intrinsic PD-1 and T cell intrinsic PD-L1 cannot be excluded (Figure 1A), since both PD-1 and PD-L1 are expressed on activated T cells.[28] Besides, when PD-1 expression level is lower than PD-L1 on tumor cells or APC, the residual PD-L1 could still mediate suppressive function via binding PD-1 on T cells in trans. This evidence concerns the gene CD274 and neoplasm.