CD80 and neoplasm: The PD-L1/B7–1 trans interaction between APC and T cells was initially reported using cell-protein interaction assays and surface plasmon resonance (Figure 1C).[31] However, later studies demonstrated that cis interaction existed between PD-L1 and B7–1 on the same cell surface of APC or tumor cells[32] and that this cis interaction relies on flexible, orientation-permissive PD-L1 on APC.[33] Another study further verified the cis interaction of PD-L1/B7–1 on the same surface of APC by using various cell co-culture, biochemistry assays, and genetic knock-in mice (Figure 1D).