Review Article | Published:

Myeloid-derived suppressor cells coming of age

Nature Immunologyvolume 19pages108119 (2018) | Download Citation



Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells generated during a large array of pathologic conditions ranging from cancer to obesity. These cells represent a pathologic state of activation of monocytes and relatively immature neutrophils. MDSCs are characterized by a distinct set of genomic and biochemical features, and can, on the basis of recent findings, be distinguished by specific surface molecules. The salient feature of these cells is their ability to inhibit T cell function and thus contribute to the pathogenesis of various diseases. In this Review, we discuss the origin and nature of these cells; their distinctive features; and their biological roles in cancer, infectious diseases, autoimmunity, obesity and pregnancy.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


  1. 1.

    Gabrilovich, D. I. et al. The terminology issue for myeloid-derived suppressor cells. Cancer Res. 67, 425 (2007).

  2. 2.

    Gabrilovich, D. I., Ostrand-Rosenberg, S. & Bronte, V. Coordinated regulation of myeloid cells by tumours. Nat. Rev. Immunol. 12, 253–268 (2012).

  3. 3.

    Dumitru, C. A., Moses, K., Trellakis, S., Lang, S. & Brandau, S. Neutrophils and granulocytic myeloid-derived suppressor cells: immunophenotyping, cell biology and clinical relevance in human oncology. Cancer Immunol. Immunother. 61, 1155–1167 (2012).

  4. 4.

    Solito, S. et al. Myeloid-derived suppressor cell heterogeneity in human cancers. Ann. NY Acad. Sci. 1319, 47–65 (2014).

  5. 5.

    Bronte, V. et al. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat. Commun. 7, 12150 (2016).

  6. 6.

    Geissmann, F. et al. Development of monocytes, macrophages, and dendritic cells. Science 327, 656–661 (2010).

  7. 7.

    Veglia, F. & Gabrilovich, D. I. Dendritic cells in cancer: the role revisited. Curr. Opin. Immunol. 45, 43–51 (2017).

  8. 8.

    Barreda, D. R., Hanington, P. C. & Belosevic, M. Regulation of myeloid development and function by colony stimulating factors. Dev. Comp. Immunol. 28, 509–554 (2004).

  9. 9.

    Marvel, D. & Gabrilovich, D. I. Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected. J. Clin. Invest. 125, 3356–3364 (2015).

  10. 10.

    Newton, K. & Dixit, V. M. Signaling in innate immunity and inflammation. Cold Spring Harb. Perspect. Biol. 4, a006049 (2012).

  11. 11.

    Kruger, P. et al. Neutrophils: between host defence, immune modulation, and tissue injury. PLoS Pathog. 11, e1004651 (2015).

  12. 12.

    Shi, C. & Pamer, E. G. Monocyte recruitment during infection and inflammation. Nat. Rev. Immunol. 11, 762–774 (2011).

  13. 13.

    Colotta, F., Allavena, P., Sica, A., Garlanda, C. & Mantovani, A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 30, 1073–1081 (2009).

  14. 14.

    Landskron, G., de la Fuente, M., Thuwajit, P., Thuwajit, C. & Hermoso, M. A. Chronic inflammation and cytokines in the tumor microenvironment. J. Immunol. Res. 2014, 149185 (2014).

  15. 15.

    Umansky, V., Blattner, C., Gebhardt, C. & Utikal, J. The role of myeloid-derived suppressor cells (MDSC) in cancer progression. Vaccines (Basel) 4, E36 (2016).

  16. 16.

    Youn, J. I., Collazo, M., Shalova, I. N., Biswas, S. K. & Gabrilovich, D. I. Characterization of the nature of granulocytic myeloid-derived suppressor cells in tumor-bearing mice. J. Leukoc. Biol. 91, 167–181 (2012).

  17. 17.

    Viale, A. et al. Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature 514, 628–632 (2014).

  18. 18.

    Ortiz, M. L., Lu, L., Ramachandran, I. & Gabrilovich, D. I. Myeloid-derived suppressor cells in the development of lung cancer. Cancer Immunol. Res. 2, 50–58 (2014).

  19. 19.

    Netea, M. G. et al. Trained immunity: a program of innate immune memory in health and disease. Science 352, aaf1098 (2016).

  20. 20.

    Condamine, T. & Gabrilovich, D. I. Molecular mechanisms regulating myeloid-derived suppressor cell differentiation and function. Trends Immunol. 32, 19–25 (2011).

  21. 21.

    Bronte, V. et al. Unopposed production of granulocyte-macrophage colony-stimulating factor by tumors inhibits CD8+ T cell responses by dysregulating antigen-presenting cell maturation. J. Immunol. 162, 5728–5737 (1999).

  22. 22.

    Dolcetti, L. et al. Hierarchy of immunosuppressive strength among myeloid-derived suppressor cell subsets is determined by GM-CSF. Eur. J. Immunol. 40, 22–35 (2010).

  23. 23.

    Umansky, V. & Sevko, A. Tumor microenvironment and myeloid-derived suppressor cells. Cancer Microenviron. 6, 169–177 (2013).

  24. 24.

    Yan, D. et al. Polyunsaturated fatty acids promote the expansion of myeloid-derived suppressor cells by activating the JAK/STAT3 pathway. Eur. J. Immunol. 43, 2943–2955 (2013).

  25. 25.

    Condamine, T., Mastio, J. & Gabrilovich, D. I. Transcriptional regulation of myeloid-derived suppressor cells. J. Leukoc. Biol. 98, 913–922 (2015).

  26. 26.

    Haverkamp, J. M. et al. Myeloid-derived suppressor activity is mediated by monocytic lineages maintained by continuous inhibition of extrinsic and intrinsic death pathways. Immunity 41, 947–959 (2014).

  27. 27.

    Ribechini, E. et al. Novel GM-CSF signals via IFN-γR/IRF-1 and AKT/mTOR license monocytes for suppressor function. Blood Advances 1, 947–960 (2017).This study demonstrates an actual example of the two-phase process in the generation of MDSCs.

  28. 28.

    Damuzzo, V. et al. Complexity and challenges in defining myeloid-derived suppressor cells. Cytometry B Clin. Cytom. 88, 77–91 (2015).This paper provides a detailed description of phenotypic characterization of MDSCs.

  29. 29.

    Fridlender, Z. G. et al. Polarization of tumor-associated neutrophil phenotype by TGF-β: “N1” versus “N2” TAN. Cancer Cell 16, 183–194 (2009).

  30. 30.

    Cimen Bozkus, C., Elzey, B. D., Crist, S. A., Ellies, L. G. & Ratliff, T. L. Expression of cationic amino acid transporter 2 is required for myeloid-derived suppressor cell-mediated control of T cell immunity. J. Immunol. 195, 5237–5250 (2015).

  31. 31.

    Mairhofer, D. G. et al. Impaired gp100-Specific CD8+ T-cell responses in the presence of myeloid-derived suppressor cells in a spontaneous mouse melanoma model. J. Invest. Dermatol. 135, 2785–2793 (2015).

  32. 32.

    Raber, P. L. et al. Subpopulations of myeloid-derived suppressor cells impair T cell responses through independent nitric oxide-related pathways. Int. J. Cancer 134, 2853–2864 (2014).

  33. 33.

    Haile, L. A., Gamrekelashvili, J., Manns, M. P., Korangy, F. & Greten, T. F. CD49d is a new marker for distinct myeloid-derived suppressor cell subpopulations in mice. J. Immunol. 185, 203–210 (2010).

  34. 34.

    Movahedi, K. et al. Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity. Blood 111, 4233–4244 (2008).

  35. 35.

    Gabrilovich, D. I. & Nagaraj, S. Myeloid-derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol. 9, 162–174 (2009).

  36. 36.

    Condamine, T. et al. Lectin-type oxidized LDL receptor-1 distinguishes population of human polymorphonuclear myeloid-derived suppressor cells in cancer patients. Sci. Immunol. 1, aaf8943 (2016).This paper describes the identification of a specific marker of human PMN-MDSCs and the possibility of converting neutrophils to PMN-MDSCs by inducing ER stress.

  37. 37.

    Mandruzzato, S. et al. Toward harmonized phenotyping of human myeloid-derived suppressor cells by flow cytometry: results from an interim study. Cancer Immunol. Immunother. 65, 161–169 (2016).

  38. 38.

    Eruslanov, E. B., Singhal, S. & Albelda, S. M. Mouse versus human neutrophils in cancer: a major knowledge gap. Trends Cancer 3, 149–160 (2017).

  39. 39.

    Fridlender, Z. G. et al. Transcriptomic analysis comparing tumor-associated neutrophils with granulocytic myeloid-derived suppressor cells and normal neutrophils. PLoS One 7, e31524 (2012).

  40. 40.

    Gato, M. et al. Drafting the proteome landscape of myeloid-derived suppressor cells. Proteomics 16, 367–378 (2016).

  41. 41.

    Gato-Cañas, M. et al. A core of kinase-regulated interactomes defines the neoplastic MDSC lineage. Oncotarget 6, 27160–27175 (2015).

  42. 42.

    Nefedova, Y. et al. Hyperactivation of STAT3 is involved in abnormal differentiation of dendritic cells in cancer. J. Immunol. 172, 464–474 (2004).

  43. 43.

    Rébé, C., Végran, F., Berger, H. & Ghiringhelli, F. STAT3 activation: a key factor in tumor immunoescape. JAK-STAT 2, e23010 (2013).

  44. 44.

    Marigo, I. et al. Tumor-induced tolerance and immune suppression depend on the C/EBPβ transcription factor. Immunity 32, 790–802 (2010).

  45. 45.

    Kumar, V. et al. CD45 phosphatase inhibits STAT3 transcription factor activity in myeloid cells and promotes tumor-associated macrophage differentiation. Immunity 44, 303–315 (2016).

  46. 46.

    Netherby, C. S. et al. The granulocyte progenitor stage is a key target of IRF8-mediated regulation of myeloid-derived suppressor cell production. J. Immunol. 198, 4129–4139 (2017).

  47. 47.

    Ramji, D. P. & Foka, P. CCAAT/enhancer-binding proteins: structure, function and regulation. Biochem. J. 365, 561–575 (2002).

  48. 48.

    Abbasi, K. et al. Concomitant carotid endarterectomy and coronary artery bypass grafting versus staged carotid stenting followed by coronary artery bypass grafting. J. Cardiovasc. Surg. (Torino) 49, 285–288 (2008).

  49. 49.

    Youn, J. I. et al. Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer. Nat. Immunol. 14, 211–220 (2013).

  50. 50.

    Casbon, A. J. et al. Invasive breast cancer reprograms early myeloid differentiation in the bone marrow to generate immunosuppressive neutrophils. Proc. Natl. Acad. Sci. USA 112, E566–E575 (2015).

  51. 51.

    Dufait, I. et al. Ex vivo generation of myeloid-derived suppressor cells that model the tumor immunosuppressive environment in colorectal cancer. Oncotarget 6, 12369–12382 (2015).

  52. 52.

    Casacuberta-Serra, S. et al. Myeloid-derived suppressor cells can be efficiently generated from human hematopoietic progenitors and peripheral blood monocytes. Immunol. Cell Biol. 95, 538–548 (2017).

  53. 53.

    Rodriguez, P. C. et al. Arginase I in myeloid suppressor cells is induced by COX-2 in lung carcinoma. J. Exp. Med. 202, 931–939 (2005).

  54. 54.

    Donkor, M. K. et al. Mammary tumor heterogeneity in the expansion of myeloid-derived suppressor cells. Int. Immunopharmacol. 9, 937–948 (2009).

  55. 55.

    Mao, Y. et al. Melanoma-educated CD14+ cells acquire a myeloid-derived suppressor cell phenotype through COX-2-dependent mechanisms. Cancer Res. 73, 3877–3887 (2013).

  56. 56.

    Hammami, I. et al. Immunosuppressive activity enhances central carbon metabolism and bioenergetics in myeloid-derived suppressor cells in vitro models. BMC Cell Biol. 13, 18 (2012).

  57. 57.

    Hossain, F. et al. Inhibition of fatty acid oxidation modulates immunosuppressive functions of myeloid-derived suppressor cells and enhances cancer therapies. Cancer Immunol. Res. 3, 1236–1247 (2015).This paper shows the involvement of lipid metabolism in the functionality of MDSCs in cancer.

  58. 58.

    Todd, D. J., Lee, A. H. & Glimcher, L. H. The endoplasmic reticulum stress response in immunity and autoimmunity. Nat. Rev. Immunol. 8, 663–674 (2008).

  59. 59.

    Grootjans, J., Kaser, A., Kaufman, R. J. & Blumberg, R. S. The unfolded protein response in immunity and inflammation. Nat. Rev. Immunol. 16, 469–484 (2016).

  60. 60.

    Cubillos-Ruiz, J. R. et al. ER stress sensor XBP1 controls anti-tumor immunity by disrupting dendritic cell homeostasis. Cell 161, 1527–1538 (2015).

  61. 61.

    Condamine, T. et al. ER stress regulates myeloid-derived suppressor cell fate through TRAIL-R-mediated apoptosis. J. Clin. Invest. 124, 2626–2639 (2014).Together with ref. 63, this study demonstrates the role of ER stress in MDSC function.

  62. 62.

    Lee, B. R. et al. Elevated endoplasmic reticulum stress reinforced immunosuppression in the tumor microenvironment via myeloid-derived suppressor cells. Oncotarget 5, 12331–12345 (2014).

  63. 63.

    Thevenot, P. T. et al. The stress-response sensor chop regulates the function and accumulation of myeloid-derived suppressor cells in tumors. Immunity 41, 389–401 (2014).Together with ref. 61, this study demonstrates the role of ER stress in MDSC function.

  64. 64.

    Dominguez, G. A. et al. Selective targeting of myeloid-derived suppressor cells in cancer patients using DS-8273a, an agonistic TRAIL-R2 antibody. Clin. Cancer Res. 23, 2942–2950 (2017).

  65. 65.

    Germano, G. et al. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell 23, 249–262 (2013).

  66. 66.

    Marini, O. et al. Identification of granulocytic myeloid-derived suppressor cells (G-MDSCs) in the peripheral blood of Hodgkin and non-Hodgkin lymphoma patients. Oncotarget 7, 27676–27688 (2016).This paper reports that mature and activated neutrophils isolated from cancer patients have suppressive functions.

  67. 67.

    Marini, O. et al. Mature CD10+ and immature CD10 neutrophils present in G-CSF-treated donors display opposite effects on T cells. Blood 129, 1343–1356 (2017).

  68. 68.

    Noy, R. & Pollard, J. W. Tumor-associated macrophages: from mechanisms to therapy. Immunity 41, 49–61 (2014).

  69. 69.

    Liu, Y. & Cao, X. The origin and function of tumor-associated macrophages. Cell. Mol. Immunol. 12, 1–4 (2015).

  70. 70.

    Ma, Y. et al. Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells. Immunity 38, 729–741 (2013).

  71. 71.

    Marigo, I. et al. T cell cancer therapy requires CD40-CD40L activation of tumor necrosis factor and inducible nitric-oxide-synthase-producing dendritic cells. Cancer Cell 30, 651 (2016).

  72. 72.

    Tesone, A. J. et al. Satb1 overexpression drives tumor-promoting activities in cancer-associated dendritic cells. Cell Rep. 14, 1774–1786 (2016).

  73. 73.

    Sun, H. L. et al. Increased frequency and clinical significance of myeloid-derived suppressor cells in human colorectal carcinoma. World J. Gastroenterol. 18, 3303–3309 (2012).

  74. 74.

    Zhang, B. et al. Circulating and tumor-infiltrating myeloid-derived suppressor cells in patients with colorectal carcinoma. PLoS One 8, e57114 (2013).

  75. 75.

    Arihara, F. et al. Increase in CD14+HLA-DR–/low myeloid-derived suppressor cells in hepatocellular carcinoma patients and its impact on prognosis. Cancer Immunol. Immunother. 62, 1421–1430 (2013).

  76. 76.

    Diaz-Montero, C. M. et al. Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol. Immunother. 58, 49–59 (2009).

  77. 77.

    Yang, G. et al. Accumulation of myeloid-derived suppressor cells (MDSCs) induced by low levels of IL-6 correlates with poor prognosis in bladder cancer. Oncotarget 8, 38378–38388 (2017).

  78. 78.

    Angell, T. E. et al. Circulating myeloid-derived suppressor cells predict differentiated thyroid cancer diagnosis and extent. Thyroid 26, 381–389 (2016).

  79. 79.

    Huang, A. et al. Increased CD14+HLA-DR–/low myeloid-derived suppressor cells correlate with extrathoracic metastasis and poor response to chemotherapy in non-small cell lung cancer patients. Cancer Immunol. Immunother. 62, 1439–1451 (2013).

  80. 80.

    Jordan, K. R. et al. Myeloid-derived suppressor cells are associated with disease progression and decreased overall survival in advanced-stage melanoma patients. Cancer Immunol. Immunother. 62, 1711–1722 (2013).

  81. 81.

    Zhang, S. et al. The role of myeloid-derived suppressor cells in patients with solid tumors: a meta-analysis. PLoS One 11, e0164514 (2016).A meta-analysis of the association between MDSC accumulation and clinical outcome in people with cancer.

  82. 82.

    Tada, K. et al. Pretreatment immune status correlates with progression-free survival in chemotherapy-treated metastatic colorectal cancer patients. Cancer Immunol. Res. 4, 592–599 (2016).

  83. 83.

    Zhang, H. et al. CXCL2/MIF-CXCR2 signaling promotes the recruitment of myeloid-derived suppressor cells and is correlated with prognosis in bladder cancer. Oncogene 36, 2095–2104 (2017).

  84. 84.

    Kawano, M. et al. The significance of G-CSF expression and myeloid-derived suppressor cells in the chemoresistance of uterine cervical cancer. Sci. Rep. 5, 18217 (2015).

  85. 85.

    Li, X. et al. Neutrophil count is associated with myeloid derived suppressor cell level and presents prognostic value of for hepatocellular carcinoma patients. Oncotarget 8, 24380–24388 (2017).

  86. 86.

    Wang, Z. et al. Tumor-induced CD14+HLA-DR–/low myeloid-derived suppressor cells correlate with tumor progression and outcome of therapy in multiple myeloma patients. Cancer Immunol. Immunother. 64, 389–399 (2015).

  87. 87.

    Wu, C. et al. Prognostic significance of peripheral monocytic myeloid-derived suppressor cells and monocytes in patients newly diagnosed with diffuse large B-cell lymphoma. Int. J. Clin. Exp. Med. 8, 15173–15181 (2015).

  88. 88.

    Galdiero, M. R. et al. Occurrence and significance of tumor-associated neutrophils in patients with colorectal cancer. Int. J. Cancer 139, 446–456 (2016).

  89. 89.

    Hurt, B., Schulick, R., Edil, B., El Kasmi, K. C. & Barnett, C. Jr. Cancer-promoting mechanisms of tumor-associated neutrophils. Am. J. Surg. 214, 938–944 (2017).

  90. 90.

    Wang, J. & Yang, J. Identification of CD4+CD25+CD127 regulatory T cells and CD14+HLA-DR–/low myeloid-derived suppressor cells and their roles in the prognosis of breast cancer. Biomed. Rep. 5, 208–212 (2016).

  91. 91.

    Chen, M. F. et al. IL-6-stimulated CD11b+CD14+HLA-DR myeloid-derived suppressor cells, are associated with progression and poor prognosis in squamous cell carcinoma of the esophagus. Oncotarget 5, 8716–8728 (2014).

  92. 92.

    Lee, S. E. et al. Circulating immune cell phenotype can predict the outcome of lenalidomide plus low-dose dexamethasone treatment in patients with refractory/relapsed multiple myeloma. Cancer Immunol. Immunother. 65, 983–994 (2016).

  93. 93.

    Romano, A. et al. Circulating myeloid-derived suppressor cells correlate with clinical outcome in Hodgkin lymphoma patients treated up-front with a risk-adapted strategy. Br. J. Haematol. 168, 689–700 (2015).

  94. 94.

    Wang, D., An, G., Xie, S., Yao, Y. & Feng, G. The clinical and prognostic significance of CD14+HLA-DR–/low myeloid-derived suppressor cells in hepatocellular carcinoma patients receiving radiotherapy. Tumour Biol. 37, 10427–10433 (2016).

  95. 95.

    Butterfield, L. H. et al. Immune correlates of GM-CSF and melanoma peptide vaccination in a randomized trial for the adjuvant therapy of resected high-risk melanoma (E4697). Clin. Cancer Res. 23, 5034–5043 (2017).

  96. 96.

    Kimura, T. et al. MUC1 vaccine for individuals with advanced adenoma of the colon: a cancer immunoprevention feasibility study. Cancer Prev. Res. (Phila.) 6, 18–26 (2013).

  97. 97.

    de Coaña, Y. P. et al. Ipilimumab treatment decreases monocytic MDSCs and increases CD8 effector memory T cells in long-term survivors with advanced melanoma. Oncotarget 8, 21539–21553 (2017).

  98. 98.

    Sade-Feldman, M. et al. Clinical significance of circulating CD33+CD11b+HLA-DR myeloid cells in patients with stage IV melanoma treated with ipilimumab. Clin. Cancer Res. 22, 5661–5672 (2016).

  99. 99.

    Martens, A. et al. Baseline peripheral blood biomarkers associated with clinical outcome of advanced melanoma patients treated with ipilimumab. Clin. Cancer Res. 22, 2908–2918 (2016).

  100. 100.

    Weber, J. et al. Phase I/II study of metastatic melanoma patients treated with nivolumab who had progressed after ipilimumab. Cancer Immunol. Res. 4, 345–353 (2016).This paper describes the association of high numbers of MDSCs with response and survival after treatment with PD-1 antibody in patients in which disease had progressed with anti-CTLA4 therapy.

  101. 101.

    Iida, Y. et al. Contrasting effects of cyclophosphamide on anti-CTL-associated protein 4 blockade therapy in two mouse tumor models. Cancer Sci. 108, 1974–1984 (2017).

  102. 102.

    Highfill, S. L. et al. Disruption of CXCR2-mediated MDSC tumor trafficking enhances anti-PD1 efficacy. Sci. Transl. Med. 6, 237ra67 (2014).A demonstration of the therapeutic effect of blocking MDSC trafficking.

  103. 103.

    Du Four, S. et al. Combined VEGFR and CTLA-4 blockade increases the antigen-presenting function of intratumoral DCs and reduces the suppressive capacity of intratumoral MDSCs. Am. J. Cancer Res. 6, 2514–2531 (2016).

  104. 104.

    Davis, R. J. et al. Anti-PD-L1 efficacy can be enhanced by inhibition of myeloid-derived suppressor cells with a selective inhibitor of PI3Kδ/γ. Cancer Res. 77, 2607–2619 (2017).This paper describes the therapeutic effect in mice after downregulation of MDSCs with PI3K inhibitor.

  105. 105.

    Lu, X. et al. Effective combinatorial immunotherapy for castration-resistant prostate cancer. Nature 543, 728–732 (2017).This study demonstrates the important role of MDSCs in a prostate cancer model, as well as the potential therapeutic benefit of targeting these cells.

  106. 106.

    Kamran, N. et al. Immunosuppressive myeloid cells’ blockade in the glioma microenvironment enhances the efficacy of immune-stimulatory gene therapy. Mol. Ther. 25, 232–248 (2017).

  107. 107.

    Ost, M. et al. Myeloid-derived suppressor cells in bacterial infections. Front. Cell. Infect. Microbiol. 6, 37 (2016).

  108. 108.

    Tebartz, C. et al. A major role for myeloid-derived suppressor cells and a minor role for regulatory T cells in immunosuppression during Staphylococcus aureus infection. J. Immunol. 194, 1100–1111 (2015).

  109. 109.

    Heim, C. E. et al. Myeloid-derived suppressor cells contribute to Staphylococcus aureus orthopedic biofilm infection. J. Immunol. 192, 3778–3792 (2014).

  110. 110.

    Dietlin, T. A. et al. Mycobacteria-induced Gr-1+ subsets from distinct myeloid lineages have opposite effects on T cell expansion. J. Leukoc. Biol. 81, 1205–1212 (2007).

  111. 111.

    Janols, H. et al. A high frequency of MDSCs in sepsis patients, with the granulocytic subtype dominating in Gram-positive cases. J. Leukoc. Biol. 96, 685–693 (2014).

  112. 112.

    Uhel, F. et al. Early expansion of circulating granulocytic myeloid-derived suppressor cells predicts development of nosocomial infections in patients with sepsis. Am. J. Respir. Crit. Care Med. 196, 315–327 (2017).

  113. 113.

    Poe, S. L. et al. STAT1-regulated lung MDSC-like cells produce IL-10 and efferocytose apoptotic neutrophils with relevance in resolution of bacterial pneumonia. Mucosal Immunol. 6, 189–199 (2013).

  114. 114.

    Rieber, N. et al. Pathogenic fungi regulate immunity by inducing neutrophilic myeloid-derived suppressor cells. Cell Host Microbe 17, 507–514 (2015).

  115. 115.

    Singh, A. et al. Differential regulation of myeloid-derived suppressor cells by Candida species. Front. Microbiol. 7, 1624 (2016).

  116. 116.

    Zhang, C. et al. Accumulation of myeloid-derived suppressor cells in the lungs during Pneumocystis pneumonia. Infect. Immun. 80, 3634–3641 (2012).

  117. 117.

    Cai, W. et al. Clinical significance and functional studies of myeloid-derived suppressor cells in chronic hepatitis C patients. J. Clin. Immunol. 33, 798–808 (2013).

  118. 118.

    Tacke, R. S. et al. Myeloid suppressor cells induced by hepatitis C virus suppress T-cell responses through the production of reactive oxygen species. Hepatology 55, 343–353 (2012).

  119. 119.

    Goh, C. C. et al. Hepatitis C virus-induced myeloid-derived suppressor cells suppress NK cell IFN-γ production by altering cellular metabolism via arginase-1. J. Immunol. 196, 2283–2292 (2016).

  120. 120.

    Goh, Y. S. et al. Bactericidal immunity to Salmonella in Africans and mechanisms causing its failure in HIV infection. PLoS Negl. Trop. Dis. 10, e0004604 (2016).

  121. 121.

    Zhai, N. et al. Hepatitis C virus induces MDSCs-like monocytes through TLR2/PI3K/AKT/STAT3 signaling. PLoS One 12, e0170516 (2017).

  122. 122.

    Qin, A. et al. Expansion of monocytic myeloid-derived suppressor cells dampens T cell function in HIV-1-seropositive individuals. J. Virol. 87, 1477–1490 (2013).

  123. 123.

    Tumino, N. et al. In HIV-positive patients, myeloid-derived suppressor cells induce T-cell anergy by suppressing CD3ζ expression through ELF-1 inhibition. AIDS 29, 2397–2407 (2015).

  124. 124.

    Garg, A. & Spector, S. A. HIV type 1 gp120-induced expansion of myeloid derived suppressor cells is dependent on interleukin 6 and suppresses immunity. J. Infect. Dis. 209, 441–451 (2014).

  125. 125.

    Wang, L. et al. Expansion of myeloid-derived suppressor cells promotes differentiation of regulatory T cells in HIV-1+ individuals. AIDS 30, 1521–1531 (2016).

  126. 126.

    Zhang, Z. N. et al. Myeloid-derived suppressor cells associated with disease progression in primary HIV infection: PD-L1 blockade attenuates inhibition. J. Acquir. Immune Defic. Syndr. 76, 200–208 (2017).

  127. 127.

    Tumino, N. et al. Granulocytic myeloid-derived suppressor cells increased in early phases of primary HIV infection depending on TRAIL plasma level. J. Acquir. Immune Defic. Syndr. 74, 575–582 (2017).

  128. 128.

    Nicholson, L. B., Raveney, B. J. & Munder, M. Monocyte dependent regulation of autoimmune inflammation. Curr. Mol. Med. 9, 23–29 (2009).

  129. 129.

    Iwata, Y. et al. Involvement of CD11b+ GR-1low cells in autoimmune disorder in MRL-Faslpr mouse. Clin. Exp. Nephrol. 14, 411–417 (2010).

  130. 130.

    Park, M. J. et al. Myeloid-derived suppressor cells induce the expansion of regulatory B cells and ameliorate autoimmunity in the sanroque mouse model of systemic lupus erythematosus. Arthritis Rheumatol. 68, 2717–2727 (2016).

  131. 131.

    Vlachou, K. et al. Elimination of granulocytic myeloid-derived suppressor cells in lupus-prone mice linked to reactive oxygen species-dependent extracellular trap formation. Arthritis Rheumatol. 68, 449–461 (2016).

  132. 132.

    Wu, H. et al. Arginase-1-dependent promotion of TH17 differentiation and disease progression by MDSCs in systemic lupus erythematosus. Sci. Transl. Med. 8, 331ra340 (2016).

  133. 133.

    Zhang, H. et al. Myeloid-derived suppressor cells are proinflammatory and regulate collagen-induced arthritis through manipulating Th17 cell differentiation. Clin. Immunol. 157, 175–186 (2015).

  134. 134.

    Guo, C. et al. Myeloid-derived suppressor cells have a proinflammatory role in the pathogenesis of autoimmune arthritis. Ann. Rheum. Dis. 75, 278–285 (2016).

  135. 135.

    Kurkó, J. et al. Identification of myeloid-derived suppressor cells in the synovial fluid of patients with rheumatoid arthritis: a pilot study. BMC Musculoskelet. Disord. 15, 281 (2014).

  136. 136.

    Egelston, C. et al. Suppression of dendritic cell maturation and T cell proliferation by synovial fluid myeloid cells from mice with autoimmune arthritis. Arthritis Rheum. 64, 3179–3188 (2012).

  137. 137.

    Jiao, Z. et al. Increased circulating myeloid-derived suppressor cells correlated negatively with Th17 cells in patients with rheumatoid arthritis. Scand. J. Rheumatol. 42, 85–90 (2013).

  138. 138.

    Guan, Q. et al. The role and potential therapeutic application of myeloid-derived suppressor cells in TNBS-induced colitis. J. Leukoc. Biol. 94, 803–811 (2013).

  139. 139.

    Kontaki, E. et al. Aberrant function of myeloid-derived suppressor cells (MDSCs) in experimental colitis and in inflammatory bowel disease (IBD) immune responses. Autoimmunity 50, 170–181 (2017).

  140. 140.

    Rader, D. J. Effect of insulin resistance, dyslipidemia, and intra-abdominal adiposity on the development of cardiovascular disease and diabetes mellitus. Am. J. Med. 120, S12–S18 (2007).

  141. 141.

    Renehan, A. G., Roberts, D. L. & Dive, C. Obesity and cancer: pathophysiological and biological mechanisms. Arch. Physiol. Biochem. 114, 71–83 (2008).

  142. 142.

    Yin, B. et al. Myeloid-derived suppressor cells prevent type 1 diabetes in murine models. J. Immunol. 185, 5828–5834 (2010).

  143. 143.

    Xia, S. et al. Gr-1+ CD11b+ myeloid-derived suppressor cells suppress inflammation and promote insulin sensitivity in obesity. J. Biol. Chem. 286, 23591–23599 (2011).

  144. 144.

    Chen, S. et al. Diminished immune response to vaccinations in obesity: role of myeloid-derived suppressor and other myeloid cells. Obes. Res. Clin. Pract. 9, 35–44 (2015).

  145. 145.

    Bao, Y., Mo, J., Ruan, L. & Li, G. Increased monocytic CD14+HLADRlow/– myeloid-derived suppressor cells in obesity. Mol. Med. Rep. 11, 2322–2328 (2015).

  146. 146.

    Quail, D. F. et al. Obesity alters the lung myeloid cell landscape to enhance breast cancer metastasis through IL5 and GM-CSF. Nat. Cell Biol. 19, 974–987 (2017).

  147. 147.

    Okwan-Duodu, D., Umpierrez, G. E., Brawley, O. W. & Diaz, R. Obesity-driven inflammation and cancer risk: role of myeloid derived suppressor cells and alternately activated macrophages. Am. J. Cancer Res. 3, 21–33 (2013).

  148. 148.

    Thomas, D. & Apovian, C. Macrophage functions in lean and obese adipose tissue. Metabolism 72, 120–143 (2017).

  149. 149.

    Lu, H. et al. Macrophages recruited via CCR2 produce insulin-like growth factor-1 to repair acute skeletal muscle injury. FASEB J. 25, 358–369 (2011).

  150. 150.

    Satoh, T. et al. The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. Nat. Immunol. 11, 936–944 (2010).

  151. 151.

    Boutens, L. & Stienstra, R. Adipose tissue macrophages: going off track during obesity. Diabetologia 59, 879–894 (2016).

  152. 152.

    Pirvulescu, M. M. et al. Subendothelial resistin enhances monocyte transmigration in a co-culture of human endothelial and smooth muscle cells by mechanisms involving fractalkine, MCP-1 and activation of TLR4 and Gi/o proteins signaling. Int. J. Biochem. Cell Biol. 50, 29–37 (2014).

  153. 153.

    Galván, G. C. et al. Effects of obesity on the regulation of macrophage population in the prostate tumor microenvironment. Nutr. Cancer 69, 996–1002 (2017).

  154. 154.

    Ghaebi, M. et al. Immune regulatory network in successful pregnancy and reproductive failures. Biomed. Pharmacother. 88, 61–73 (2017).

  155. 155.

    Fainaru, O., Hantisteanu, S. & Hallak, M. Immature myeloid cells accumulate in mouse placenta and promote angiogenesis. Am. J. Obstet. Gynecol. 204, 544.e518–544.e23 (2011).

  156. 156.

    Pan, T. et al. Myeloid-derived suppressor cells are essential for maintaining feto-maternal immunotolerance via STAT3 signaling in mice. J. Leukoc. Biol. 100, 499–511 (2016).Together with ref. 160, this study demonstrates the role of MDSCs in the maintenance of feto-maternal tolerance.

  157. 157.

    Kang, X. et al. CXCR2-mediated granulocytic myeloid-derived suppressor cells’ functional characterization and their role in maternal fetal interface. DNA Cell Biol. 35, 358–365 (2016).

  158. 158.

    Pan, T. et al. 17β-Oestradiol enhances the expansion and activation of myeloid-derived suppressor cells via signal transducer and activator of transcription (STAT)-3 signalling in human pregnancy. Clin. Exp. Immunol. 185, 86–97 (2016).

  159. 159.

    Kang, X. et al. Granulocytic myeloid-derived suppressor cells maintain feto-maternal tolerance by inducing Foxp3 expression in CD4+CD25 T cells by activation of the TGF-β/β-catenin pathway. Mol. Hum. Reprod. 22, 499–511 (2016).

  160. 160.

    Ostrand-Rosenberg, S. et al. Frontline science: myeloid-derived suppressor cells (MDSCs) facilitate maternal-fetal tolerance in mice. J. Leukoc. Biol. 101, 1091–1101 (2017).Together with ref. 156, this study demonstrates the role of MDSCs in the maintenance of feto-maternal tolerance.

  161. 161.

    Gantt, S., Gervassi, A., Jaspan, H. & Horton, H. The role of myeloid-derived suppressor cells in immune ontogeny. Front. Immunol. 5, 387 (2014).

  162. 162.

    Bartmann, C. et al. CD33+/HLA-DRneg and CD33+/HLA-DR+/– cells: rare populations in the human decidua with characteristics of MDSC. Am. J. Reprod. Immunol. 75, 539–556 (2016).

  163. 163.

    Köstlin, N. et al. Granulocytic myeloid derived suppressor cells expand in human pregnancy and modulate T-cell responses. Eur. J. Immunol. 44, 2582–2591 (2014).

  164. 164.

    Nair, R. R., Sinha, P., Khanna, A. & Singh, K. Reduced myeloid-derived suppressor cells in the blood and endometrium is associated with early miscarriage. Am. J. Reprod. Immunol. 73, 479–486 (2015).

  165. 165.

    Kim, Y. J. et al. Reduced L-arginine level and decreased placental eNOS activity in preeclampsia. Placenta 27, 438–444 (2006).

  166. 166.

    Zhang, Y. et al. Human trophoblast cells induced MDSCs from peripheral blood CD14+ myelomonocytic cells via elevated levels of CCL2. Cell. Mol. Immunol. 13, 615–627 (2016).

  167. 167.

    Gervassi, A. et al. Myeloid derived suppressor cells are present at high frequency in neonates and suppress in vitro T cell responses. PLoS One 9, e107816 (2014).

  168. 168.

    Rieber, N. et al. Neutrophilic myeloid-derived suppressor cells in cord blood modulate innate and adaptive immune responses. Clin. Exp. Immunol. 174, 45–52 (2013).

  169. 169.

    Köstlin, N. et al. Granulocytic myeloid-derived suppressor cells from human cord blood modulate T-helper cell response towards an anti-inflammatory phenotype. Immunology 152, 89–101 (2017).

  170. 170.

    Leiber, A. et al. Neonatal myeloid derived suppressor cells show reduced apoptosis and immunosuppressive activity upon infection with Escherichia coli. Eur. J. Immunol. 47, 1009–1021 (2017).

  171. 171.

    Heinemann, A. S. et al. In neonates S100A8/S100A9 alarmins prevent the expansion of a specific inflammatory monocyte population promoting septic shock. FASEB J. 31, 1153–1164 (2017).

  172. 172.

    Ulas, T. et al. S100-alarmin-induced innate immune programming protects newborn infants from sepsis. Nat. Immunol. 18, 622–632 (2017).

Download references


This work was supported by the US National Institutes of Health (grants CA084488 and CA100062 to D.G.). We thank R. Kim for help with the preparation of the manuscript.

Author information

Author notes

  1. Filippo Veglia and Michela Perego contributed equally to this work.


  1. The Wistar Institute, Philadelphia, PA, USA

    • Filippo Veglia
    • , Michela Perego
    •  & Dmitry Gabrilovich


  1. Search for Filippo Veglia in:

  2. Search for Michela Perego in:

  3. Search for Dmitry Gabrilovich in:

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Dmitry Gabrilovich.

About this article

Publication history





Further reading