Abstract
Myeloid-derived suppressor cells strongly expand in many pathological conditions including cancer, and they suppress immunological responses by interfering with the effector functions of T cells, dendritic cells, and NK cells. The differentiation and accumulation of MDSCs is a negative outcome caused by the interplay between tumor cells and myelopoiesis. Since the phenotype of MDSCs and their mechanisms of action seem to depend on the type of cancer and stage of the disease, it is important to evaluate which MDSC subsets have prognostic values in the outcome of the disease. In the present chapter we will systematize the current information on the different populations of human MDSCs and their markers as well as their similarities/differences with MDSCs from murine models.
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References
Youn JI, Kumar V, Collazo M, Nefedova Y, Condamine T, Cheng P, Villagra A, Antonia S, McCaffrey JC, Fishman M, Sarnaik A, Horna P, Sotomayor E, Gabrilovich DI (2013) Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer. Nat Immunol 14(3):211ā220. doi:10.1038/ni.2526 ni.2526 [pii]
Liechtenstein T, Perez-Janices N, Gato M, Caliendo F, Kochan G, Blanco-Luquin I, Van der Jeught K, Arce F, Guerrero-Setas D, Fernandez-Irigoyen J, Santamaria E, Breckpot K, Escors D (2014) A highly efficient tumor-infiltrating MDSC differentiation system for discovery of anti-neoplastic targets, which circumvents the need for tumor establishment in mice. Oncotarget 5(17):7843ā7857
Bronte V, Wang M, Overwijk WW, Surman DR, Pericle F, Rosenberg SA, Restifo NP (1998) Apoptotic death of CD8+ T lymphocytes after immunization: induction of a suppressive population of Mac-1+/Gr-1+ cells. J Immunol 161(10):5313ā5320
Kusmartsev S, Gabrilovich DI (2002) Immature myeloid cells and cancer-associated immune suppression. Cancer Immunol Immunother 51(6):293ā298
Bronte V, Chappell DB, Apolloni E, Cabrelle A, Wang M, Hwu P, Restifo NP (1999) Unopposed production of granulocyte-macrophage colony-stimulating factor by tumors inhibits CD8+ T cell responses by dysregulating antigen-presenting cell maturation. J Immunol 162(10):5728ā5737
Haile LA, Gamrekelashvili J, Manns MP, Korangy F, Greten TF (2010) CD49d is a new marker for distinct myeloid-derived suppressor cell subpopulations in mice. J Immunol 185(1):203ā210. doi:10.4049/jimmunol.0903573
Mandruzzato S, Solito S, Falisi E, Francescato S, Chiarion-Sileni V, Mocellin S, Zanon A, Rossi CR, Nitti D, Bronte V, Zanovello P (2009) IL4Ralpha+ myeloid-derived suppressor cell expansion in cancer patients. J Immunol 182(10):6562ā6568. doi:10.4049/jimmunol.0803831
Rodriguez PC, Ernstoff MS, Hernandez C, Atkins M, Zabaleta J, Sierra R, Ochoa AC (2009) Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res 69(4):1553ā1560. doi:10.1158/0008-5472.CAN-08-1921
Eruslanov E, Neuberger M, Daurkin I, Perrin GQ, Algood C, Dahm P, Rosser C, Vieweg J, Gilbert SM, Kusmartsev S (2012) Circulating and tumor-infiltrating myeloid cell subsets in patients with bladder cancer. Int J Cancer 130(5):1109ā1119. doi:10.1002/ijc.26123
Gielen PR, Schulte BM, Kers-Rebel ED, Verrijp K, Petersen-Baltussen HM, ter Laan M, Wesseling P, Adema GJ (2015) Increase in both CD14-positive and CD15-positive myeloid-derived suppressor cell subpopulations in the blood of patients with glioma but predominance of CD15-positive myeloid-derived suppressor cells in glioma tissue. J Neuropathol Exp Neurol 74(5):390ā400. doi:10.1097/NEN.0000000000000183
Vasquez-Dunddel D, Pan F, Zeng Q, Gorbounov M, Albesiano E, Fu J, Blosser RL, Tam AJ, Bruno T, Zhang H, Pardoll D, Kim Y (2013) STAT3 regulates arginase-I in myeloid-derived suppressor cells from cancer patients. J Clin Invest 123(4):1580ā1589. doi:10.1172/JCI60083
Brandau S, Trellakis S, Bruderek K, Schmaltz D, Steller G, Elian M, Suttmann H, Schenck M, Welling J, Zabel P, Lang S (2011) Myeloid-derived suppressor cells in the peripheral blood of cancer patients contain a subset of immature neutrophils with impaired migratory properties. J Leukoc Biol 89(2):311ā317. doi:10.1189/jlb.0310162
Filipazzi P, Valenti R, Huber V, Pilla L, Canese P, Iero M, Castelli C, Mariani L, Parmiani G, Rivoltini L (2007) Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients with modulation by a granulocyte-macrophage colony-stimulation factor-based antitumor vaccine. J Clin Oncol 25(18):2546ā2553. doi:10.1200/JCO.2006.08.5829
Tarhini AA, Butterfield LH, Shuai Y, Gooding WE, Kalinski P, Kirkwood JM (2012) Differing patterns of circulating regulatory T cells and myeloid-derived suppressor cells in metastatic melanoma patients receiving anti-CTLA4 antibody and interferon-alpha or TLR-9 agonist and GM-CSF with peptide vaccination. J Immunother 35(9):702ā710. doi:10.1097/CJI.0b013e318272569b
Kohanbash G, McKaveney K, Sakaki M, Ueda R, Mintz AH, Amankulor N, Fujita M, Ohlfest JR, Okada H (2013) GM-CSF promotes the immunosuppressive activity of glioma-infiltrating myeloid cells through interleukin-4 receptor-alpha. Cancer Res 73(21):6413ā6423. doi:10.1158/0008-5472.CAN-12-4124
Napolitano M, DāAlterio C, Cardone E, Trotta AM, Pecori B, Rega D, Pace U, Scala D, Scognamiglio G, Tatangelo F, Cacciapuoti C, Pacelli R, Delrio P, Scala S (2015) Peripheral myeloid-derived suppressor and T regulatory PD-1 positive cells predict response to neoadjuvant short-course radiotherapy in rectal cancer patients. Oncotarget 6(10):8261ā8270
Wang L, Chang EW, Wong SC, Ong SM, Chong DQ, Ling KL (2013) Increased myeloid-derived suppressor cells in gastric cancer correlate with cancer stage and plasma S100A8/A9 proinflammatory proteins. J Immunol 190(2):794ā804. doi:10.4049/jimmunol.1202088
Gros A, Turcotte S, Wunderlich JR, Ahmadzadeh M, Dudley ME, Rosenberg SA (2012) Myeloid cells obtained from the blood but not from the tumor can suppress T-cell proliferation in patients with melanoma. Clin Cancer Res 18(19):5212ā5223. doi:10.1158/1078-0432.CCR-12-1108
Diaz-Montero CM, Salem ML, Nishimura MI, Garrett-Mayer E, Cole DJ, Montero AJ (2009) Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother 58(1):49ā59. doi:10.1007/s00262-008-0523-4
Gehad AE, Lichtman MK, Schmults CD, Teague JE, Calarese AW, Jiang Y, Watanabe R, Clark RA (2012) Nitric oxide-producing myeloid-derived suppressor cells inhibit vascular E-selectin expression in human squamous cell carcinomas. J Invest Dermatol 132(11):2642ā2651. doi:10.1038/jid.2012.190
Rodriguez PC, Ochoa AC (2008) Arginine regulation by myeloid derived suppressor cells and tolerance in cancer: mechanisms and therapeutic perspectives. Immunol Rev 222:180ā191. doi:10.1111/j.1600-065X.2008.00608.x
Srivastava MK, Sinha P, Clements VK, Rodriguez P, Ostrand-Rosenberg S (2010) Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine. Cancer Res 70(1):68ā77
Corzo CA, Cotter MJ, Cheng P, Cheng F, Kusmartsev S, Sotomayor E, Padhya T, McCaffrey TV, McCaffrey JC, Gabrilovich DI (2009) Mechanism regulating reactive oxygen species in tumor-induced myeloid-derived suppressor cells. J Immunol 182(9):5693ā5701
Yu J, Du W, Yan F, Wang Y, Li H, Cao S, Yu W, Shen C, Liu J, Ren X (2013) Myeloid-derived suppressor cells suppress antitumor immune responses through IDO expression and correlate with lymph node metastasis in patients with breast cancer. J Immunol 190(7):3783ā3797. doi:10.4049/jimmunol.1201449 jimmunol.1201449 [pii]
Chevolet I, Speeckaert R, Schreuer M, Neyns B, Krysko O, Bachert C, Hennart B, Allorge D, van Geel N, Van Gele M, Brochez L (2015) Characterization of the immune network of IDO, tryptophan metabolism, PD-L1, and in circulating immune cells in melanoma. Oncoimmunology 4(3):e982382. doi:10.4161/2162402X.2014.982382
Novitskiy SV, Pickup MW, Gorska AE, Owens P, Chytil A, Aakre M, Wu H, Shyr Y, Moses HL (2011) TGF-beta receptor II loss promotes mammary carcinoma progression by Th17 dependent mechanisms. Cancer Discov 1(5):430ā441. doi:10.1158/2159-8290.CD-11-0100
Yang L, Huang J, Ren X, Gorska AE, Chytil A, Aakre M, Carbone DP, Matrisian LM, Richmond A, Lin PC, Moses HL (2008) Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+ CD11b+ myeloid cells that promote metastasis. Cancer Cell 13(1):23ā35. doi:10.1016/j.ccr.2007.12.004
Condamine T, Ramachandran I, Youn JI, Gabrilovich DI (2015) Regulation of tumor metastasis by myeloid-derived suppressor cells. Ann Rev Med 66:97ā110. doi:10.1146/annurev-med-051013-052304
Lechner MG, Liebertz DJ, Epstein AL (2010) Characterization of cytokine-induced myeloid-derived suppressor cells from normal human peripheral blood mononuclear cells. J Immunol 185(4):2273ā2284. doi:10.4049/jimmunol.1000901 jimmunol.1000901 [pii]
Valenti R, Huber V, Filipazzi P, Pilla L, Sovena G, Villa A, Corbelli A, Fais S, Parmiani G, Rivoltini L (2006) Human tumor-released microvesicles promote the differentiation of myeloid cells with transforming growth factor-beta-mediated suppressive activity on T lymphocytes. Cancer Res 66(18):9290ā9298
Gato-CaƱas M, Martinez de Morentin X, Blanco-Luquin I, Fernandez-Irigoyen J, Zudaire I, Liechtenstein T, Arasanz H, Lozano T, Casares N, Knapp S, Chaikuad A, Guerrero-Setas D, Escors D, Kochan G, Santamaria E (2015) A core of kinase-regulated interactomes defines the neoplastic MDSC lineage. Oncotarget (In press)
Boutte AM, McDonald WH, Shyr Y, Yang L, Lin PC (2011) Characterization of the MDSC proteome associated with metastatic murine mammary tumors using label-free mass spectrometry and shotgun proteomics. PLoS ONE 6(8):e22446. doi:10.1371/journal.pone.0022446
Chornoguz O, Grmai L, Sinha P, Artemenko KA, Zubarev RA, Ostrand-Rosenberg S (2011) Proteomic pathway analysis reveals inflammation increases myeloid-derived suppressor cell resistance to apoptosis. Mol Cell Proteomics10(3):M110 002980. doi:10.1074/mcp.M110.002980
Acknowledgments
Grazyna Kochan research is funded by a CAIXA project grant from the, Spain, a Sandra Ibarra research grant, and a Gobierno Vasco BioEf project grant (BIO13/CI/014).
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Kochan, G. (2016). Human MDSCs. In: Myeloid-Derived Suppressor Cells and Cancer. SpringerBriefs in Immunology. Springer, Cham. https://doi.org/10.1007/978-3-319-26821-7_3
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DOI: https://doi.org/10.1007/978-3-319-26821-7_3
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