We provide evidence that iron supplementation contributes to the upregulation of PD-L1 expression in antigen-presenting cells, cancer cells, etc. Although we examined the impact of iron-mediated PD-L1 upregulation in macrophages on T cell activation, which in turn hampers anticancer therapy, other factors may determine the efficacy of anti-PD-L1 therapy. This evidence concerns the gene CD274 and cancer.