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Roles of Myeloid-Derived Suppressor Cells in Cancer Metastasis: Immunosuppression and Beyond

  • Amin Pastaki Khoshbin
  • Mahsa Eskian
  • Mahsa Keshavarz-Fathi
  • Nima RezaeiEmail author
Review
  • 334 Downloads

Abstract

Metastasis is the direst face of cancer, and it is not a feature solely dependent on cancer cells; however, a complex interaction between cancer cells and host causes this process. Investigating the mechanisms of metastasis can lead to its control. Myeloid-derived suppressor cells (MDSCs) are key components of tumor microenvironment that favor cancer progression. These cells result from altered myelopoiesis in response to the presence of tumor. The most recognized function of MDSCs is suppressing anti-tumor immune responses. Strikingly, these cells are among important players in cancer dissemination and metastasis. They can exert their effect on metastatic process by affecting anti-cancer immunity, epithelial–mesenchymal transition, cancer stem cell formation, angiogenesis, establishing premetastatic niche, and supporting cancer cell survival and growth in metastatic sites. In this article, we review and discuss the mechanisms by which MDSCs contribute to cancer metastasis.

Keywords

Myeloid-derived suppressor cells Metastasis Immunosuppression Premetastatic niche Angiogenesis Apoptosis 

Notes

Acknowledgements

We would like to thank Dr. Susanna Mandruzzato from Oncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy, for evaluation of the manuscript and her expert comments to improve the paper.

Compliance with ethical standards

Conflict of interest

The authors declare they had no conflicts of interest.

References

  1. Beury DW, Parker KH, Nyandjo M et al (2014) Cross-talk among myeloid-derived suppressor cells, macrophages, and tumor cells impacts the inflammatory milieu of solid tumors. J Leukoc Biol 96:1109–1118PubMedPubMedCentralCrossRefGoogle Scholar
  2. Bianchi G, Borgonovo G, Pistoia V et al (2011) Immunosuppressive cells and tumour microenvironment: focus on mesenchymal stem cells and myeloid derived suppressor cells. Histol Histopathol 26:941–951PubMedGoogle Scholar
  3. Binsfeld M, Muller J, Lamour V et al (2016) Granulocytic myeloid-derived suppressor cells promote angiogenesis in the context of multiple myeloma. Oncotarget 7:37931–37943PubMedPubMedCentralCrossRefGoogle Scholar
  4. Bodogai M, Moritoh K, Lee-Chang C et al (2015) Immunosuppressive and prometastatic functions of myeloid-derived suppressive cells rely upon education from tumor-associated B cells. Cancer Res 75:3456–3465PubMedPubMedCentralCrossRefGoogle Scholar
  5. Boutte AM, Friedman DB, Bogyo M et al (2011) Identification of a myeloid-derived suppressor cell cystatin-like protein that inhibits metastasis. FASEB J 25:2626–2637PubMedPubMedCentralCrossRefGoogle Scholar
  6. Bronte V, Brandau S, Chen SH et al (2016) Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun 7:12150PubMedPubMedCentralCrossRefGoogle Scholar
  7. Catena R, Bhattacharya N, El Rayes T et al (2013) Bone marrow-derived Gr1 + cells can generate a metastasis-resistant microenvironment via induced secretion of thrombospondin-1. Cancer Discov 3:578–589PubMedPubMedCentralCrossRefGoogle Scholar
  8. Chafe SC, Lou Y, Sceneay J et al (2015) Carbonic anhydrase IX promotes myeloid-derived suppressor cell mobilization and establishment of a metastatic niche by stimulating G-CSF production. Cancer Res 75:996–1008PubMedCrossRefGoogle Scholar
  9. Chen X, Wang L, Li P et al (2018) Dual TGF-beta and PD-1 blockade synergistically enhances MAGE-A3-specific CD8(+) T cell response in esophageal squamous cell carcinoma. Int J Cancer.  https://doi.org/10.1002/ijc.31730 CrossRefPubMedPubMedCentralGoogle Scholar
  10. Chiang AC, Massagué J (2008) Molecular basis of metastasis. N Engl J Med 359:2814–2823PubMedPubMedCentralCrossRefGoogle Scholar
  11. Choi HS, Ha SY, Kim HM et al (2016) The prognostic effects of tumor infiltrating regulatory T cells and myeloid derived suppressor cells assessed by multicolor flow cytometry in gastric cancer patients. Oncotarget 7:7940–7951PubMedPubMedCentralGoogle Scholar
  12. Condamine T, Ramachandran I, Youn JI et al (2015) Regulation of tumor metastasis by myeloid-derived suppressor cells. Annu Rev Med 66:97–110PubMedCrossRefGoogle Scholar
  13. Condamine T, Dominguez GA, Youn JI et al (2016) Lectin-type oxidized LDL receptor-1 distinguishes population of human polymorphonuclear myeloid-derived suppressor cells in cancer patients. Sci Immunol 1(2):aaf8943PubMedPubMedCentralCrossRefGoogle Scholar
  14. Connolly MK, Mallen-St Clair J, Bedrosian AS et al (2010) Distinct populations of metastases-enabling myeloid cells expand in the liver of mice harboring invasive and preinvasive intra-abdominal tumor. J Leukoc Biol 87:713–725PubMedCrossRefGoogle Scholar
  15. Costa-Silva B, Aiello NM, Ocean AJ et al (2015) Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol 17:816–826PubMedPubMedCentralCrossRefGoogle Scholar
  16. Cui TX, Kryczek I, Zhao L et al (2013) Myeloid-derived suppressor cells enhance stemness of cancer cells by inducing microRNA101 and suppressing the corepressor CtBP2. Immunity 39:611–621PubMedCrossRefPubMedCentralGoogle Scholar
  17. Dang CV (1999) c-Myc target genes involved in cell growth, apoptosis, and metabolism. Mol Cell Biol 19:1–11PubMedPubMedCentralCrossRefGoogle Scholar
  18. Deng J, Liu Y, Lee H et al (2012) S1PR1-STAT3 signaling is crucial for myeloid cell colonization at future metastatic sites. Cancer Cell 21:642–654PubMedPubMedCentralCrossRefGoogle Scholar
  19. Deng Z, Rong Y, Teng Y et al (2017) Exosomes miR-126a released from MDSC induced by DOX treatment promotes lung metastasis. Oncogene 36:639–651PubMedCrossRefGoogle Scholar
  20. Drews-Elger K, Iorns E, Dias A et al (2014) Infiltrating S100A8 + myeloid cells promote metastatic spread of human breast cancer and predict poor clinical outcome. Breast Cancer Res Treat 148:41–59PubMedCrossRefGoogle Scholar
  21. Eisenblaetter M, Flores-Borja F, Lee JJ et al (2017) Visualization of tumor-immune interaction - target-specific imaging of S100A8/A9 reveals pre-metastatic niche establishment. Theranostics 7:2392–2401PubMedPubMedCentralCrossRefGoogle Scholar
  22. Erler JT, Bennewith KL, Cox TR et al (2009) Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell 15:35–44PubMedPubMedCentralCrossRefGoogle Scholar
  23. Finke J, Ko J, Rini B et al (2011) MDSC as a mechanism of tumor escape from sunitinib mediated anti-angiogenic therapy. Int Immunopharmacol 11:856–861PubMedCrossRefGoogle Scholar
  24. Fortini ME (2009) Notch signaling: the core pathway and its posttranslational regulation. Dev Cell 16:633–647PubMedCrossRefGoogle Scholar
  25. Gao D, Joshi N, Choi H et al (2012) Myeloid progenitor cells in the premetastatic lung promote metastases by inducing mesenchymal to epithelial transition. Cancer Res 72:1384–1394PubMedCrossRefGoogle Scholar
  26. Giles AJ, Reid CM, Evans JD et al (2016) Activation of hematopoietic stem/progenitor cells promotes immunosuppression within the pre-metastatic niche. Cancer Res 76:1335–1347PubMedCrossRefGoogle Scholar
  27. Guo Y, Xu F, Lu T et al (2012) Interleukin-6 signaling pathway in targeted therapy for cancer. Cancer Treat Rev 38:904–910PubMedCrossRefGoogle Scholar
  28. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674PubMedCrossRefGoogle Scholar
  29. Hiratsuka S, Watanabe A, Aburatani H et al (2006) Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat Cell Biol 8:1369–1375PubMedCrossRefGoogle Scholar
  30. Hiratsuka S, Watanabe A, Sakurai Y et al (2008) The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. Nat Cell Biol 10:1349–1355PubMedCrossRefGoogle Scholar
  31. Hoechst B, Voigtlaender T, Ormandy L et al (2009) Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor. Hepatology 50:799–807PubMedPubMedCentralCrossRefGoogle Scholar
  32. Hwang HC, Clurman BE (2005) Cyclin E in normal and neoplastic cell cycles. Oncogene 24:2776–2786PubMedCrossRefGoogle Scholar
  33. Ichikawa M, Williams R, Wang L et al (2011) S100A8/A9 activate key genes and pathways in colon tumor progression. Mol Cancer Res 9:133–148PubMedPubMedCentralCrossRefGoogle Scholar
  34. Iwata T, Kondo Y, Kimura O et al (2016) PD-L1(+)MDSCs are increased in HCC patients and induced by soluble factor in the tumor microenvironment. Sci Rep 6:39296PubMedPubMedCentralCrossRefGoogle Scholar
  35. Jiang J, Guo W, Liang X (2014) Phenotypes, accumulation, and functions of myeloid-derived suppressor cells and associated treatment strategies in cancer patients. Hum Immunol 75:1128–1137PubMedCrossRefGoogle Scholar
  36. Kalluri R, Weinberg RA (2009) The basics of epithelial–mesenchymal transition. J Clin Invest 119:1420–1428PubMedPubMedCentralCrossRefGoogle Scholar
  37. Kaplan RN, Riba RD, Zacharoulis S et al (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438:820–827PubMedPubMedCentralCrossRefGoogle Scholar
  38. Ko JS, Rayman P, Ireland J et al (2010) Direct and differential suppression of myeloid-derived suppressor cell subsets by sunitinib is compartmentally constrained. Cancer Res 70:3526–3536PubMedPubMedCentralCrossRefGoogle Scholar
  39. Kowanetz M, Wu X, Lee J et al (2010) Granulocyte-colony stimulating factor promotes lung metastasis through mobilization of Ly6G+ Ly6C+ granulocytes. Proc Natl Acad Sci USA 107:21248–21255PubMedCrossRefGoogle Scholar
  40. Kujawski M, Kortylewski M, Lee H et al (2008) Stat3 mediates myeloid cell–dependent tumor angiogenesis in mice. J Clin Invest 118:3367–3377PubMedPubMedCentralCrossRefGoogle Scholar
  41. Leber MF, Efferth T (2009) Molecular principles of cancer invasion and metastasis (review). Int J Oncol 34:881–895PubMedGoogle Scholar
  42. Lee JM, Seo JH, Kim YJ et al (2012) The restoration of myeloid-derived suppressor cells as functional antigen-presenting cells by NKT cell help and all-trans-retinoic acid treatment. Int J Cancer 131:741–751PubMedCrossRefGoogle Scholar
  43. Lee JM, Kim EK, Seo H et al (2014) Serum amyloid A3 exacerbates cancer by enhancing the suppressive capacity of myeloid-derived suppressor cells via TLR2-dependent STAT3 activation. Eur J Immunol 44:1672–1684PubMedCrossRefGoogle Scholar
  44. Li F, Tiede B, Massagué J et al (2007) Beyond tumorigenesis: cancer stem cells in metastasis. Cell Res 17:3–14PubMedCrossRefGoogle Scholar
  45. Li ZL, Ye SB, OuYang LY et al (2015) COX-2 promotes metastasis in nasopharyngeal carcinoma by mediating interactions between cancer cells and myeloid-derived suppressor cells. Oncoimmunology 4:e1044712PubMedPubMedCentralCrossRefGoogle Scholar
  46. Lim SY, Gordon-Weeks A, Allen D et al (2015) Cd11b(+) myeloid cells support hepatic metastasis through down-regulation of angiopoietin-like 7 in cancer cells. Hepatology 62:521–533PubMedCrossRefGoogle Scholar
  47. Lindau D, Gielen P, Kroesen M et al (2013) The immunosuppressive tumour network: myeloid-derived suppressor cells, regulatory T cells and natural killer T cells. Immunology 138:105–115PubMedPubMedCentralCrossRefGoogle Scholar
  48. Lu C, Redd PS, Lee JR et al (2016) The expression profiles and regulation of PD-L1 in tumor-induced myeloid-derived suppressor cells. Oncoimmunology 5:e1247135PubMedPubMedCentralCrossRefGoogle Scholar
  49. Maruhashi T, Kii I, Saito M et al (2010) Interaction between periostin and BMP-1 promotes proteolytic activation of lysyl oxidase. J Biol Chem 285:13294–13303PubMedPubMedCentralCrossRefGoogle Scholar
  50. Marvel D, Gabrilovich DI (2015) Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected. J Clin Invest 125:3356–3364PubMedPubMedCentralCrossRefGoogle Scholar
  51. Mauti LA, Le Bitoux MA, Baumer K et al (2011) Myeloid-derived suppressor cells are implicated in regulating permissiveness for tumor metastasis during mouse gestation. J Clin Invest 121:2794–2807PubMedPubMedCentralCrossRefGoogle Scholar
  52. Moserle L, Casanovas O (2013) Anti-angiogenesis and metastasis: a tumour and stromal cell alliance. J Intern Med 273:128–137PubMedCrossRefGoogle Scholar
  53. Motallebnezhad M, Jadidi-Niaragh F, Qamsari ES et al (2016) The immunobiology of myeloid-derived suppressor cells in cancer. Tumour Biol 37:1387–1406PubMedCrossRefGoogle Scholar
  54. Mucha J, Majchrzak K, Taciak B et al (2014) MDSCs mediate angiogenesis and predispose canine mammary tumor cells for metastasis via IL-28/IL-28RA (IFN-λ) signaling. PLoS One 9:e103249PubMedPubMedCentralCrossRefGoogle Scholar
  55. Murdoch C, Muthana M, Coffelt SB et al (2008) The role of myeloid cells in the promotion of tumour angiogenesis. Nat Rev Cancer 8:618–631PubMedCrossRefGoogle Scholar
  56. Noman MZ, Desantis G, Janji B et al (2014) PD-L1 is a novel direct target of HIF-1alpha, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med 211:781–790PubMedPubMedCentralCrossRefGoogle Scholar
  57. Obermajer N, Muthuswamy R, Lesnock J et al (2011) Positive feedback between PGE2 and COX2 redirects the differentiation of human dendritic cells toward stable myeloid-derived suppressor cells. Blood 118:5498–5505PubMedPubMedCentralCrossRefGoogle Scholar
  58. Oh K, Lee OY, Shon SY et al (2013) A mutual activation loop between breast cancer cells and myeloid-derived suppressor cells facilitates spontaneous metastasis through IL-6 trans-signaling in a murine model. Breast Cancer Res 15:R79PubMedPubMedCentralCrossRefGoogle Scholar
  59. Olechnowicz SW, Edwards CM (2014) Contributions of the host microenvironment to cancer-induced bone disease. Cancer Res 74:1625–1631PubMedPubMedCentralCrossRefGoogle Scholar
  60. Oskarsson T, Batlle E, Massagué J (2014) Metastatic stem cells: sources, niches, and vital pathways. Cell Stem Cell 14:306–321PubMedPubMedCentralCrossRefGoogle Scholar
  61. Ostrand-Rosenberg S, Sinha P, Beury DW et al (2012) Cross-talk between myeloid-derived suppressor cells (MDSC), macrophages, and dendritic cells enhances tumor-induced immune suppression. Semin Cancer Biol 22:275–281PubMedPubMedCentralCrossRefGoogle Scholar
  62. Ouzounova M, Lee E, Piranlioglu R et al (2017) Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumour plasticity during metastatic cascade. Nat Commun 8:14979PubMedPubMedCentralCrossRefGoogle Scholar
  63. Pan PY, Ma G, Weber KJ et al (2010) Immune stimulatory receptor CD40 is required for T-cell suppression and T regulatory cell activation mediated by myeloid-derived suppressor cells in cancer. Cancer Res 70:99–108PubMedCrossRefGoogle Scholar
  64. Panni RZ, Sanford DE, Belt BA et al (2014) Tumor-induced STAT3 activation in monocytic myeloid-derived suppressor cells enhances stemness and mesenchymal properties in human pancreatic cancer. Cancer Immunol Immunother 63:513–528PubMedPubMedCentralCrossRefGoogle Scholar
  65. Papaccio F, Paino F, Regad T et al (2017) Concise review: cancer cells, cancer stem cells, and mesenchymal stem cells: influence in cancer development. Stem Cells Transl Med 6:2115–2125PubMedPubMedCentralCrossRefGoogle Scholar
  66. Park YJ, Song B, Kim YS et al (2013) Tumor microenvironmental conversion of natural killer cells into myeloid-derived suppressor cells. Cancer Res 73:5669–5681PubMedCrossRefGoogle Scholar
  67. Pruenster M, Vogl T, Roth J et al (2016) S100A8/A9: from basic science to clinical application. Pharmacol Ther 167:120–131PubMedCrossRefGoogle Scholar
  68. Qu X, Zhuang G, Yu L et al (2012) Induction of Bv8 expression by granulocyte colony-stimulating factor in CD11b+ Gr1+ cells: key role of Stat3 signaling. J Biol Chem 287:19574–19584PubMedPubMedCentralCrossRefGoogle Scholar
  69. Rose-John S (2012) IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6. Int J Biol Sci 8:1237–1247PubMedPubMedCentralCrossRefGoogle Scholar
  70. Rutkowski MR, Stephen TL, Svoronos N et al (2015) Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation. Cancer Cell 27:27–40PubMedCrossRefGoogle Scholar
  71. Sanchez-Tillo E, de Barrios O, Siles L et al (2011) beta-catenin/TCF4 complex induces the epithelial-to-mesenchymal transition (EMT)-activator ZEB1 to regulate tumor invasiveness. Proc Natl Acad Sci USA 108:19204–19209PubMedCrossRefGoogle Scholar
  72. Sangaletti S, Tripodo C, Sandri S et al (2014) Osteopontin shapes immunosuppression in the metastatic niche. Cancer Res 74:4706–4719PubMedCrossRefGoogle Scholar
  73. Sato Y, Shimizu K, Shinga J et al (2015) Characterization of the myeloid-derived suppressor cell subset regulated by NK cells in malignant lymphoma. Oncoimmunology 4:e995541PubMedPubMedCentralCrossRefGoogle Scholar
  74. Sawant A, Deshane J, Jules J et al (2013) Myeloid-derived suppressor cells function as novel osteoclast progenitors enhancing bone loss in breast cancer. Cancer Res 73:672–682PubMedCrossRefGoogle Scholar
  75. Sceneay J, Chow MT, Chen A et al (2012) Primary tumor hypoxia recruits CD11b+/Ly6Cmed/Ly6G+ immune suppressor cells and compromises NK cell cytotoxicity in the premetastatic niche. Cancer Res 72:3906–3911PubMedCrossRefGoogle Scholar
  76. Seshadri M, Poduval TB, Sundaram K (1979) Studies on metastases. I. Role of sensitization and immunosuppression. J Natl Cancer Inst 63:1205–1210PubMedGoogle Scholar
  77. Shaw AK, Pickup MW, Chytil A et al (2015) TGFβ signaling in myeloid cells regulates mammary carcinoma cell invasion through fibroblast interactions. PLoS One 10:e0117908PubMedPubMedCentralCrossRefGoogle Scholar
  78. Shen T, Zhou L, Shen H et al (2017) Prognostic value of programmed cell death protein 1 expression on CD8+ T lymphocytes in pancreatic cancer. Sci Rep 7:7848PubMedPubMedCentralCrossRefGoogle Scholar
  79. Shen M, Wang J, Yu W et al (2018) A novel MDSC-induced PD-1(−)PD-L1(+) B-cell subset in breast tumor microenvironment possesses immuno-suppressive properties. Oncoimmunology 7:e1413520PubMedPubMedCentralCrossRefGoogle Scholar
  80. Shi Y, Ou L, Han S et al (2014) Deficiency of Kruppel-like factor KLF4 in myeloid-derived suppressor cells inhibits tumor pulmonary metastasis in mice accompanied by decreased fibrocytes. Oncogenesis 3:e129PubMedPubMedCentralCrossRefGoogle Scholar
  81. Shi H, Zhang J, Han X et al (2017) Recruited monocytic myeloid-derived suppressor cells promote the arrest of tumor cells in the premetastatic niche through an IL-1beta-mediated increase in E-selectin expression. Int J Cancer 140:1370–1383PubMedCrossRefGoogle Scholar
  82. Shiels MS, Copeland G, Goodman MT et al (2015) Cancer stage at diagnosis in patients infected with the human immunodeficiency virus and transplant recipients. Cancer 121:2063–2071PubMedPubMedCentralCrossRefGoogle Scholar
  83. Shojaei F, Wu X, Zhong C et al (2007a) Bv8 regulates myeloid-cell-dependent tumour angiogenesis. Nature 450:825–831PubMedCrossRefGoogle Scholar
  84. Shojaei F, Wu X, Malik AK et al (2007b) Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+ Gr1+ myeloid cells. Nat Biotechnol 25:911–920PubMedCrossRefGoogle Scholar
  85. Shojaei F, Wu X, Qu X et al (2009) G-CSF-initiated myeloid cell mobilization and angiogenesis mediate tumor refractoriness to anti-VEGF therapy in mouse models. Proc Natl Acad Sci USA 106:6742–6747PubMedCrossRefGoogle Scholar
  86. Sinha P, Clements VK, Bunt SK et al (2007) Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J Immunol 179:977–983PubMedCrossRefGoogle Scholar
  87. Sinha P, Okoro C, Foell D et al (2008) Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells. J Immunol 181:4666–4675PubMedPubMedCentralCrossRefGoogle Scholar
  88. Solito S, Pinton L, Mandruzzato S (2017) In brief: myeloid-derived suppressor cells in cancer. J Pathol 242:7–9PubMedPubMedCentralCrossRefGoogle Scholar
  89. Song J, Lee J, Kim J et al (2016) Pancreatic adenocarcinoma up-regulated factor (PAUF) enhances the accumulation and functional activity of myeloid-derived suppressor cells (MDSCs) in pancreatic cancer. Oncotarget 7:51840–51853PubMedPubMedCentralGoogle Scholar
  90. Stacker SA, Achen MG, Jussila L et al (2002) Lymphangiogenesis and cancer metastasis. Nat Rev Cancer 2:573–583PubMedCrossRefGoogle Scholar
  91. Steeg PS (2016) Targeting metastasis. Nat Rev Cancer 16:201–218PubMedCrossRefGoogle Scholar
  92. Supuran CT, Winum JY (2015) Carbonic anhydrase IX inhibitors in cancer therapy: an update. Future Med Chem 7:1407–1414PubMedCrossRefGoogle Scholar
  93. Terai S, Fushida S, Tsukada T et al (2015) Bone marrow derived “fibrocytes” contribute to tumor proliferation and fibrosis in gastric cancer. Gastric Cancer 18:306–313PubMedCrossRefGoogle Scholar
  94. Thorn M, Point GR, Burga RA et al (2014) Liver metastases induce reversible hepatic B cell dysfunction mediated by Gr-1+ CD11b+ myeloid cells. J Leukoc Biol 96:883–894PubMedPubMedCentralCrossRefGoogle Scholar
  95. Toh B, Wang X, Keeble J et al (2011) Mesenchymal transition and dissemination of cancer cells is driven by myeloid-derived suppressor cells infiltrating the primary tumor. PLoS Biol 9:e1001162PubMedPubMedCentralCrossRefGoogle Scholar
  96. Topalian SL, Drake CG, Pardoll DM (2015) Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell 27:450–461PubMedPubMedCentralCrossRefGoogle Scholar
  97. Ugel S, De Sanctis F, Mandruzzato S et al (2015) Tumor-induced myeloid deviation: when myeloid-derived suppressor cells meet tumor-associated macrophages. J Clin Invest 125:3365–3376PubMedPubMedCentralCrossRefGoogle Scholar
  98. Umansky V, Blattner C, Gebhardt C et al (2016) The role of myeloid-derived suppressor cells (MDSC) in cancer progression. Vaccines 4:E36PubMedCrossRefGoogle Scholar
  99. Vadrevu SK, Chintala NK, Sharma SK et al (2014) Complement c5a receptor facilitates cancer metastasis by altering T-cell responses in the metastatic niche. Cancer Res 74:3454–3465PubMedCrossRefGoogle Scholar
  100. van Deventer HW, Palmieri DA, Wu QP et al (2013) Circulating fibrocytes prepare the lung for cancer metastasis by recruiting Ly-6C+ monocytes via CCL2. J Immunol 190:4861–4867PubMedPubMedCentralCrossRefGoogle Scholar
  101. Vrakas CN, O’Sullivan RM, Evans SE et al (2015) The measure of DAMPs and a role for S100A8 in recruiting suppressor cells in breast cancer lung metastasis. Immunol Invest 44:174–188PubMedCrossRefGoogle Scholar
  102. Wang L, Chang EW, Wong SC et al (2013) Increased myeloid-derived suppressor cells in gastric cancer correlate with cancer stage and plasma S100A8/A9 proinflammatory proteins. J Immunol 190:794–804PubMedCrossRefGoogle Scholar
  103. Wang Z, Xiong S, Mao Y et al (2016) Periostin promotes immunosuppressive premetastatic niche formation to facilitate breast tumour metastasis. J Pathol 239:484–495PubMedCrossRefGoogle Scholar
  104. Wang D, Sun H, Wei J et al (2017a) CXCL1 is critical for pre-metastatic niche formation and metastasis in colorectal cancer. Cancer Res 77:3655–3665PubMedPubMedCentralCrossRefGoogle Scholar
  105. Wang Q, Liu F, Liu L (2017b) Prognostic significance of PD-L1 in solid tumor: an updated meta-analysis. Medicine (Baltimore) 96:e6369CrossRefGoogle Scholar
  106. Welcker M, Clurman BE (2008) FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation. Nat Rev Cancer 8:83–93PubMedCrossRefGoogle Scholar
  107. Wen SW, Sceneay J, Lima LG et al (2016) The biodistribution and immune suppressive effects of breast cancer-derived exosomes. Cancer Res 76:6816–6827PubMedCrossRefGoogle Scholar
  108. Wong CC, Gilkes DM, Zhang H et al (2011) Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation. Proc Natl Acad Sci USA 108:16369–16374PubMedCrossRefGoogle Scholar
  109. Wyczechowska D et al (2015) Isolation and characterization of human MDSC from peripheral blood of patients with various malignancies (TUM6P. 971). J Immunol 194(1 Supplement):141.119–141.119Google Scholar
  110. Yamashita YM, Yuan H, Cheng J et al (2010) Polarity in stem cell division: asymmetric stem cell division in tissue homeostasis. Cold Spring Harb Perspect Biol 2:a001313PubMedPubMedCentralCrossRefGoogle Scholar
  111. Yan J, Huang J (2014) Innate γδT17 cells convert cancer-elicited inflammation into immunosuppression through myeloid-derived suppressor cells. Oncoimmunology 3:e953423PubMedPubMedCentralCrossRefGoogle Scholar
  112. Yan HH, Pickup M, Pang Y et al (2010) Gr-1+ CD11b+ myeloid cells tip the balance of immune protection to tumor promotion in the premetastatic lung. Cancer Res 70:6139–6149PubMedPubMedCentralCrossRefGoogle Scholar
  113. Yan HH, Jiang J, Pang Y et al (2015) CCL9 induced by TGFbeta signaling in myeloid cells enhances tumor cell survival in the premetastatic organ. Cancer Res 75:5283–5298PubMedPubMedCentralCrossRefGoogle Scholar
  114. Yang L, DeBusk LM, Fukuda K et al (2004) Expansion of myeloid immune suppressor Gr+ CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell 6:409–421PubMedCrossRefGoogle Scholar
  115. Yang L, Huang J, Ren X et al (2008) Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+ CD11b+ myeloid cells that promote metastasis. Cancer Cell 13:23–35PubMedPubMedCentralCrossRefGoogle Scholar
  116. Ye XZ, Yu SC, Bian XW (2010) Contribution of myeloid-derived suppressor cells to tumor-induced immune suppression, angiogenesis, invasion and metastasis. J Genet Genomics 37:423–430PubMedCrossRefGoogle Scholar
  117. Yumimoto K, Akiyoshi S, Ueo H et al (2015) F-box protein FBXW7 inhibits cancer metastasis in a non-cell-autonomous manner. J Clin Invest 125:621–635PubMedPubMedCentralCrossRefGoogle Scholar
  118. Zhang B, Wang Z, Wu L et al (2013a) Circulating and tumor-infiltrating myeloid-derived suppressor cells in patients with colorectal carcinoma. PLoS One 8:e57114PubMedPubMedCentralCrossRefGoogle Scholar
  119. Zhang H, Maric I, DiPrima MJ et al (2013b) Fibrocytes represent a novel MDSC subset circulating in patients with metastatic cancer. Blood 122:1105–1113PubMedPubMedCentralCrossRefGoogle Scholar
  120. Zhang G, Huang H, Zhu Y et al (2015a) A novel subset of B7-H3+ CD14+ HLA-DR-/low myeloid-derived suppressor cells are associated with progression of human NSCLC. Oncoimmunology 4:e977164PubMedPubMedCentralCrossRefGoogle Scholar
  121. Zhang X, Yuan X, Shi H et al (2015b) Exosomes in cancer: small particle, big player. J Hematol Oncol 8:83PubMedPubMedCentralCrossRefGoogle Scholar
  122. Zhang Y, Velez-Delgado A, Mathew E et al (2017) Myeloid cells are required for PD-1/PD-L1 checkpoint activation and the establishment of an immunosuppressive environment in pancreatic cancer. Gut 66:124–136PubMedCrossRefGoogle Scholar
  123. Zhao T, Du H, Ding X et al (2015) Activation of mTOR pathway in myeloid-derived suppressor cells stimulates cancer cell proliferation and metastasis in lal(−/−) mice. Oncogene 34:1938–1948PubMedCrossRefGoogle Scholar
  124. Zhao T, Du H, Blum JS et al (2016a) Critical role of PPARgamma in myeloid-derived suppressor cell-stimulated cancer cell proliferation and metastasis. Oncotarget 7:1529–1543PubMedGoogle Scholar
  125. Zhao T, Yan C, Du H (2016b) Lysosomal acid lipase in mesenchymal stem cell stimulation of tumor growth and metastasis. Oncotarget 7:61121–61135PubMedPubMedCentralGoogle Scholar
  126. Zheng R, Chen S, Chen S (2015) Correlation between myeloid-derived suppressor cells and S100A8/A9 in tumor and autoimmune diseases. Int Immunopharmacol 29:919–925PubMedCrossRefGoogle Scholar

Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2018

Authors and Affiliations

  • Amin Pastaki Khoshbin
    • 1
    • 2
  • Mahsa Eskian
    • 1
    • 3
    • 4
  • Mahsa Keshavarz-Fathi
    • 1
    • 2
    • 3
    • 5
  • Nima Rezaei
    • 3
    • 4
    • 6
    • 7
    Email author
  1. 1.Cancer Immunology Project (CIP)Universal Scientific Education and Research Network (USERN)TehranIran
  2. 2.School of MedicineTehran University of Medical SciencesTehranIran
  3. 3.Research Center for Immunodeficiencies, Children’s Medical CenterTehran University of Medical SciencesTehranIran
  4. 4.Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA)Universal Scientific Education and Research Network (USERN)TehranIran
  5. 5.Breast Cancer Association (BrCA)Universal Scientific Education and Research Network (USERN)TehranIran
  6. 6.Department of Immunology, School of MedicineTehran University of Medical SciencesTehranIran
  7. 7.Cancer Immunology Project (CIP)Universal Scientific Education and Research Network (USERN)SheffieldUK

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