Growing evidence suggests that ligation of PD-L1 could transmit reverse signaling to T cells or tumor cells.[29,30] It was recently reported that in a pancreatic tumor model, tumor-infiltrating T cells expressed high levels of PD-L1, which could provide bi-directional signaling via PD-1/PD-L1 axis.[30] In this setting, since most activated T cells already express PD-1, it is not clear whether PD-L1 expressed by the same T cells would function as a ligand or a receptor (Figure 1B). Here, CD274 is linked to neoplasm.