CD274 and metabolic disease: A number of key events, such as transcriptional reprogramming, epigenetic modifications and metabolic disorders, have been demonstrated to promote leukocyte tolerance (reduced cytokine production and impaired antigen presentation), increase the expression of inhibitory checkpoint molecules (e.g., programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T - lymphocyte antigen 4 CTLA-1) or suppressive immune cells (e.g., regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs)) and induce anergy or death in lymphocytes (8, 14).