Long-term administration of PD-1 antibodies led to significant increase of risks for autoimmune diseases (e.g., type 1 diabetes), which was due to that PD-1 mAb treatment abrogated endogenous signaling axis of PD-L1/PD-1, thereby pathogenically activated autoreactive T cells and ultimately caused the onset of autoimmune diseases (33–35); (b) PD-1 expression is limited to activated T and B cells as well as myeloid cells, implying that PD-L1/PD-1 signals is an important brake to avoid excessive immune response. This evidence concerns the gene CD274 and type 1 diabetes mellitus.