Fig. 1From: Targeting PD-1/PD-L1 pathway in myelodysplastic syndromes and acute myeloid leukemiaFunction of dysregulated PD-1/PD-L1 pathway in MDS. Upon exposure to IFN-γ and TNF-α, PD-L1 levels are increased in MDS blasts via NF-κB and pSTAT1/pSTAT3 activation. Further, TP53 mutation also implicated in PD-L1 upregulation via MYC upregulation and miR-34a downregulation, thus regulating PD-L1 levels at a post-transcriptional level. In CD34+ HSPCs, TP53 mutation and S100A9 upregulate PD-1 via MYC. Furthermore, PD-L1+ MDS blasts mediate pathogenesis through PD-1/PD-L1 signaling, by the following mechanisms: ①blasts expressing PD-L1 confer proliferative advantages, expressing higher levels of CyclinD1/D2/D3 and growing more actively; ② the binding of PD-L1 on MDS blasts with PD-1 on CD34+ HSPCs result in PD-1+CD34+ HSPC apoptosis. ③ the binding of PD-L1 on MDS blasts with PD-1 on CD4+/CD8+ T cells inhibit the activation and proliferation of these effector T cells. MHC, major histocompatibility complex; TNFR, TNF receptor; MT, mutation; pSTAT, phosphorylated signal transducer and activator of transcriptionBack to article page