Strikingly, here our studies revealed nontraditional roles (i.e., non-T-cell-specific) for PD-1 and PD-L1 in MDS, where S100A9 contributes to ineffective hematopoiesis in MDS via induction of PD-1 and PD-L1 expression. This evidence concerns the gene CD274 and myelodysplastic syndrome.