Myeloid-Derived Suppressor Cell Dynamics in Tumor Immunology

Myeloid-derived suppressor cells (MDSCs) are a diverse assemblage of immature myeloid cells that expand during tumour progression and chronic inflammation. Originating from aberrant myelopoiesis in the bone marrow and extramedullary sites such as the spleen, MDSCs comprise monocytic and granulocytic subsets that orchestrate potent immunosuppression. Through depletion of key metabolites, release of reactive oxygen and nitrogen species, secretion of immunoregulatory cytokines and induction of regulatory T cells, MDSCs inhibit cytotoxic T-cell and natural killer-cell functions, foster tumour angiogenesis and establish pre-metastatic niches. Their dynamic accumulation and plasticity underpin resistance to chemotherapy, radiotherapy and immune checkpoint blockade. As understanding of MDSC ontogeny and mechanism deepens, novel interventions targeting their recruitment, differentiation and suppressive pathways offer promising routes to enhance anti-tumour immunity and improve patient outcomes.

Research from Nature Portfolio

Recent studies have refined minimal reporting guidelines for murine and human MDSC characterisation, standardising phenotypic markers and functional assays to improve interstudy comparability. Investigations in hepatocellular carcinoma have elucidated hypoxia-driven stabilisation of hypoxia-inducible factor-1, which upregulates ectonucleoside triphosphate diphosphohydrolase 2 (ENTPD2) and impedes MDSC differentiation, thereby sustaining immunosuppressive populations within tumours. Further work has delineated distinct kinetics and mechanisms of monocytic and granulocytic MDSC subsets during metastatic progression, revealing that monocytic cells foster epithelial–mesenchymal transition at primary sites while granulocytic subsets support colonisation and growth at distant organs.

Myeloid-Derived Suppressor Cell Dynamics in Tumor Immunology publication trend

The graph below shows the total number of articles in myeloid-derived suppressor cell dynamics in tumor immunology across all publications each year (not limited to Nature Index journals).

Technical terms

Myeloid-Derived Suppressor Cells (MDSCs): Heterogeneous population of immature myeloid cells that accumulate during cancer and chronic inflammation and suppress T-cell responses.

Monocytic MDSC (mMDSC): MDSC subset derived from monocyte precursors, characterised by distinct surface markers and potent immunosuppressive functions.

Polymorphonuclear MDSC (PMN-MDSC): Granulocytic MDSC subset resembling neutrophils, implicated in tumour progression and pre-metastatic niche formation.

Tumour microenvironment (TME): Complex milieu of cancer cells, stromal components and immune cells that influences tumour growth and therapy response.

Epithelial–mesenchymal transition (EMT): Biological process by which epithelial cells acquire mesenchymal characteristics, enhancing motility and invasiveness.

Immune checkpoint inhibitors (ICI): Therapeutic antibodies that block inhibitory pathways on T cells, restoring anti-tumour immunity.

Hypoxia-inducible factor-1 (HIF-1): Transcription factor stabilised under low oxygen conditions, regulating genes involved in angiogenesis and cell survival.

References

1. Overcoming resistance to immunotherapy by targeting GPR84 in myeloid-derived suppressor cells. Signal Transduction and Targeted Therapy (2023).
2. Bladder-cancer-derived exosomal circRNA_0013936 promotes suppressive immunity by up-regulating fatty acid transporter protein 2 and down-regulating receptor-interacting protein kinase 3 in PMN-MDSCs. Molecular Cancer (2024).
3. Tumor-associated myeloid cells in cancer immunotherapy. Journal of Hematology & Oncology (2023).
4. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nature Communications (2016).
5. Immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) during tumour progression. British Journal of Cancer (2018).
6. Myeloid-Derived Suppressor Cells Hinder the Anti-Cancer Activity of Immune Checkpoint Inhibitors. Frontiers in Immunology (2018).
7. Targeting Myeloid-Derived Suppressor Cells to Bypass Tumor-Induced Immunosuppression. Frontiers in Immunology (2018).
8. Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer. Signal Transduction and Targeted Therapy (2021).
9. Hypoxia inducible factor HIF-1 promotes myeloid-derived suppressor cells accumulation through ENTPD2/CD39L1 in hepatocellular carcinoma. Nature Communications (2017).
10. Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumour plasticity during metastatic cascade. Nature Communications (2017).