ArticleLeukemia2019
S100A9-induced overexpression of PD-1/PD-L1 contributes to ineffective hematopoiesis in myelodysplastic syndromes.
Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 100 citations in OpenAlex.
- Sintilimab plus decitabine for higher-risk treatment-naïve myelodysplastic syndromes: efficacy, safety, and biomarker analysis of a phase II, single-arm trial.Journal for immunotherapy of cancer · 2024Trial
- Targeting TGFBR1 with the Investigational Inhibitor TP-6379 Improves Hematopoiesis in Low-Risk MDS Ex Vivo.Cells · 2026Article
- Bone marrow immunosuppressive states associate with survival after guadecitabine and atezolizumab therapy in HMA-R/R MDS.Blood neoplasia · 2026Article
- High frequency of CD95British journal of haematology · 2026Article
- Preclinical efficacy of tasquinimod in myelodysplastic neoplasms: Restoring erythropoiesis and mitigating bone loss.HemaSphere · 2026Article
- Low-input proteomics identifies vWF as a negative regulator of Tet2 mutant hematopoietic stem cell expansion.Cell reports · 2026Article
- Myeloid-derived suppressor cells in multiple myeloma: mechanistic insights and therapeutic implications.Frontiers in immunology · 2026Review
- Myeloid-Derived Suppressor Cells: Immunoregulatory Roles and Therapeutic Prospects in Immune-Mediated Hematological Disorders.Journal of immunology research · 2026Review
- S100A9 regulates eosinophil extracellular trap and activates NF-κB signaling in endometrial cancer: a machine learning-based biomarker discovery.Cancer cell international · 2025Article
- Dendritic Cells of Leukemic Origin (DCCancers · 2025Article
- Targeting Calprotectin S100A8/A9 to Overcome AML Progression in DNMT3A-Mutant Cells.Current medical science · 2025Article
- Bone marrow microenvironment in myelodysplastic neoplasms: insights into pathogenesis, biomarkers, and therapeutic targets.Cancer cell international · 2025Review
- MDSC checkpoint blockade therapy: a new breakthrough point overcoming immunosuppression in cancer immunotherapy.Cancer gene therapy · 2025Review
- Innate immune-inflammatory signaling milieu in myeloid leukemia and aging-associated clonal hematopoiesis pathologies.Frontiers in immunology · 2025Review
- Optimizing single cell RNA sequencing of stem cells. A streamlined workflow for enhanced sensitivity and reproducibility in hematopoietic studies. The use of human umbilical cord blood-derived hematopoietic stem and progenitor cells.Frontiers in cell and developmental biology · 2025Article
- Multifaceted Aspects of Dysfunctional Myelopoiesis in Cancer and Therapeutic Perspectives with Focus on HCC.Biomolecules · 2024Review
- Bone marrow inflammation in haematological malignancies.Nature reviews. Immunology · 2024Review
- Myeloid-derived suppressor cells-induced exhaustion of CD8 + T-cell participates in rejection after liver transplantation.Cell death & disease · 2024Article
- Immune-monitoring of myelodysplastic neoplasms: Recommendations from the i4MDS consortium.HemaSphere · 2024Article
- Unraveling T cell exhaustion in the immune microenvironment of osteosarcoma via single-cell RNA transcriptome.Cancer immunology, immunotherapy : CII · 2024Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Myelodysplastic syndromes (MDS) are characterized by dysplastic and ineffective hematopoiesis that can result from aberrant expansion and activation of myeloid-derived suppressor cells (MDSCs) within the bone marrow (BM) niche. MDSCs produce S100A9, which mediates premature death of hematopoietic stem and progenitor cells (HSPCs). The PD-1/PD-L1 immune checkpoint impairs immune responses by inducing T-cell exhaustion and apoptosis, but its role in MDS is uncharacterized. Here we report an increased expression of PD-1 on HSPCs and PD-L1 on MDSCs in MDS versus healthy donors, and that this checkpoint is also activated in S100A9 transgenic (S100A9Tg) mice, and by treatment of BM mononuclear cells (BM-MNC) with S100A9. Further, MDS BM-MNC treated with recombinant PD-L1 underwent cell death, suggesting that the PD-1/PD-L1 interaction contributes to HSPC death in MDS. In accordance with this notion, PD-1/PD-L1 blockade restores effective hematopoiesis and improves colony-forming capacity in BM-MNC from MDS patients. Similar findings were observed in aged S100A9Tg mice. Finally, we demonstrate that c-Myc is required for S100A9-induced upregulation of PD-1/PD-L1, and that treatment of MDS HSPCs with anti-PD-1 antibody suppresses the expression of Myc target genes and increases the expression of hematopoietic pathway genes. We conclude anti-PD-1/anti-PD-L1 blocking strategies offer therapeutic promise in MDS in restoring effective hematopoiesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.