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Tumor-Associated Macrophages and Myeloid-Derived Suppressor Cells as Immunosuppressive Mechanism in Ovarian Cancer Patients: Progress and Challenges

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Pages 372-385 | Received 17 Jun 2015, Accepted 22 Jun 2016, Published online: 19 Sep 2016

REFERENCES

  • Scarlett UK, Conejo-Garcia JR. Modulating the tumor immune microenvironment as an ovarian cancer treatment strategy. Expert Rev Obstet Gynecol. 2012;7(5):413–419.
  • Davidson B, Tropé CG. Ovarian cancer: diagnostic, biological and prognostic aspects. Womens Health 2014;10(5):519–533.
  • Charbonneau B, Goode EL, Kalli KR, The immune system in the pathogenesis of ovarian cancer. Crit Rev Immunol 2013;33(2):137–164.
  • Balkwill FR, Capasso M, Hagemann T. The tumor microenvironment at a glance. J Cell Sci 2012;125(23):5591–5596.
  • Wertel I, Nowicka A, Rogala E, Peritoneal immune system in patients with advance epithelial ovarian cancer. Int Rev Immunol 2011;30(2-3):87–101.
  • Peng D-J, Liu R, Zou W. Regulatory T cells in human ovarian cancer. J Oncol 2012;2012:345164.
  • Goyne HE, Cannon MJ. Dendritic cell vaccination, immune regulation, and clinical outcomes in ovarian cancer. Front Immunol 2013;4:382
  • Lavoué V, Thédrez A, Levêque J, Immunity of human epithelial ovarian carcinoma: the paradigm of immune suppression in cancer. J Transl Med 2013;11:147.
  • Khaled YS, Ammori BJ, Elkord E. Myeloid-derived suppressor cells in cancer: recent progress and prospects. Immunol Cell Biol 2013;91(8):493–502.
  • Solito S, Marigo I, Pinton L, Myeloid-derived suppressor cell heterogeneity in human cancers. Ann N Y AcadSci 2014;1319(1):47–65.
  • Jiang J, Guo W, Liang X. Phenotypes, accumulation, and functions of myeloid-derived suppressor cells and associated treatment strategies in cancer patients. Hum Immunol 2014;75(11):1128–1137.
  • Heusinkveld M, Burg SH van der. Identification and manipulation of tumor associated macrophages in human cancers. J Transl Med 2011;9:216.
  • Diaz-Montero CM, Salem ML, Nishimura MI, Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother 2009;58(1):49–59.
  • Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol 2008;8(12):958–969.
  • Rigo A, Gottardi M, Zamò A, Macrophages may promote cancer growth via a GM-CSF/HB-EGF paracrine loop that is enhanced by CXCL12. Mol Cancer 2010;9:273.
  • Sánchez-Martín L, Estecha A, Samaniego R, The chemokine CXCL12 regulates monocyte-macrophage differentiation and RUNX3 expression. Blood 2011;117(1):88–97.
  • Niino D, Komohara Y, Murayama T, Ratio of M2 macrophage expression is closely associated with poor prognosis for Angioimmunoblastic T-cell lymphoma (AITL). Pathol Int 2010;60(4):278–283.
  • Steidl C, Lee T, Shah SP, Tumor-associated macrophages and survival in classic Hodgkin's lymphoma. N Engl J Med 2010;362(10):875–885.
  • Tzankov A, Matter MS, Dirnhofer S. Refined prognostic role of CD68-positive tumor macrophages in the context of the cellular micromilieu of classical Hodgkin lymphoma. Pathobiol J Immunopathol Mol Cell Biol 2010;77(6):301–308.
  • Bronkhorst IHG, Ly LV, Jordanova ES, Detection of M2-macrophages in uveal melanoma and relation with survival. Invest Ophthalmol Vis Sci 2011;52(2):643–650.
  • Jensen TO, Schmidt H, Møller HJ, Macrophage markers in serum and tumor have prognostic impact in American Joint Committee on Cancer stage I/II melanoma. J Clin Oncol 2009;27(20):3330–3337.
  • Komohara Y, Ohnishi K, Kuratsu J, Possible involvement of the M2 anti-inflammatory macrophage phenotype in growth of human gliomas. J Pathol 2008;216(1):15–24.
  • Stout RD, Jiang C, Matta B, Macrophages sequentially change their functional phenotype in response to changes in microenvironmental influences. J Immunol 2005;175(1):342–349.
  • Forssell J, Oberg A, Henriksson ML, High macrophage infiltration along the tumor front correlates with improved survival in colon cancer. Clin Cancer Res 2007;13(5):1472–1479.
  • Algars A, Irjala H, Vaittinen S, Type and location of tumor-infiltrating macrophages and lymphatic vessels predict survival of colorectal cancer patients. Int J Cancer 2012;131(4):864–873.
  • Kang J-C, Chen J-S, Lee C-H, Intratumoral macrophage counts correlate with tumor progression in colorectal cancer. J Surg Oncol 2010;102(3):242–248.
  • Ma J, Liu L, Che G, The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time. BMC Cancer 2010;10:112.
  • Dai F, Liu L, Che G, The number and microlocalization of tumor-associated immune cells are associated with patient's survival time in non-small cell lung cancer. BMC Cancer 2010;10:220.
  • Ohri CM, Shikotra A, Green RH, Macrophages within NSCLC tumour islets are predominantly of a cytotoxic M1 phenotype associated with extended survival. Eur Respir J 2009;33(1):118–126.
  • Zeni E, Mazzetti L, Miotto D, Macrophage expression of interleukin-10 is a prognostic factor in nonsmall cell lung cancer. Eur Respir J 2007;30(4):627–632.
  • Tang X. Tumor-associated macrophages as potential diagnostic and prognostic biomarkers in breast cancer. Cancer Lett 2013;332(1):3–10.
  • Campbell MJ, Tonlaar NY, Garwood ER, Proliferating macrophages associated with high grade, hormone receptor negative breast cancer and poor clinical outcome. Breast Cancer Res Treat 2011;128(3):703–711.
  • Chen J, Yao Y, Gong C, CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PITPNM3. Cancer Cell 2011;19(4):541–555.
  • Shabo I, Stål O, Olsson H, Breast cancer expression of CD163, a macrophage scavenger receptor, is related to early distant recurrence and reduced patient survival. Int J Cancer 2008;123(4):780–786.
  • Caillou B, Talbot M, Weyemi U, Tumor-associated macrophages (TAMs) form an interconnected cellular supportive network in anaplastic thyroid carcinoma. PloS One 2011;6(7):e22567.
  • Ryder M, Ghossein RA, Ricarte-Filho JCM, Increased density of tumor-associated macrophages is associated with decreased survival in advanced thyroid cancer. Endocr Relat Cancer 2008;15(4):1069–1074.
  • Espinosa I, José Carnicer M, Catasus L, Myometrial invasion and lymph node metastasis in endometrioid carcinomas: tumor-associated macrophages, microvessel density, and HIF1A have a crucial role. Am J Surg Pathol 2010;34(11):1708–1714.
  • Yang X, Dong Y, Zhao J, Increased expression of human macrophage metalloelastase (MMP-12) is associated with the invasion of endometrial adenocarcinoma. Pathol Res Pract 2007;203(7):499–505.
  • Nonomura N, Takayama H, Nakayama M, Infiltration of tumour-associated macrophages in prostate biopsy specimens is predictive of disease progression after hormonal therapy for prostate cancer. BJU Int 2011;107(12):1918–1922.
  • Takayama H, Nonomura N, Nishimura K, Decreased immunostaining for macrophage scavenger receptor is associated with poor prognosis of prostate cancer. BJU Int 2009;103(4):470–474.
  • Osinsky S, Bubnovskaya L, Ganusevich I, Hypoxia, tumour-associated macrophages, microvessel density, VEGF and matrix metalloproteinases in human gastric cancer: interaction and impact on survival. Clin Transl Oncol 2011;13(2):133–138.
  • Shirabe K, Mano Y, Muto J, Role of tumor-associated macrophages in the progression of hepatocellular carcinoma. Surg Today 2012;42(1):1–7.
  • Toge H, Inagaki T, Kojimoto Y, Angiogenesis in renal cell carcinoma: the role of tumor-associated macrophages. Int J Urol 2009;16(10):801–807.
  • Ajili F, Kourda N, Darouiche A, Prognostic value of tumor-associated macrophages count in human non-muscle-invasive bladder cancer treated by BCG immunotherapy. Ultrastruct Pathol 2013;37(1):56–61.
  • Kurahara H, Shinchi H, Mataki Y, Significance of M2-polarized tumor-associated macrophage in pancreatic cancer. J Surg Res 2011;167(2):e211–219.
  • Kawamura K, Komohara Y, Takaishi K, Detection of M2 macrophages and colony-stimulating factor 1 expression in serous and mucinous ovarian epithelial tumors. Pathol Int 2009;59(5):300–305.
  • Bailey C, Negus R, Morris A, Chemokine expression is associated with the accumulation of tumour associated macrophages (TAMs) and progression in human colorectal cancer. Clin Exp Metastasis 2007;24(2):121–130.
  • Kryczek I, Zou L, Rodriguez P, B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J Exp Med 2006;203(4):871–881.
  • Postow MA, Callahan MK, Barker CA, Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med 2012;366(10):925–931.
  • Poschke I, Mougiakakos D, Hansson J, Immature immunosuppressive CD14+HLA-DR−/low cells in melanoma patients are Stat3hi and overexpress CD80, CD83, and DC-sign. Cancer Res 2010;70(11):4335–4345.
  • Vasquez-Dunddel D, Pan F, Zeng Q, STAT3 regulates arginase-I in myeloid-derived suppressor cells from cancer patients. J Clin Invest 2013;123(4):1580–1589.
  • Huang A, Zhang B, Wang B, 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 2013;62(9):1439–1451.
  • Hoechst B, Ormandy LA, Ballmaier M, A new population of myeloid-derived suppressor cells in hepatocellular carcinoma patients induces CD4(+)CD25(+)Foxp(3+) T cells. Gastroenterology 2008;135(1):234–243.
  • Arihara F, Mizukoshi E, Kitahara M, Increase in CD14+HLA-DR−/low myeloid-derived suppressor cells in hepatocellular carcinoma patients and its impact on prognosis. Cancer Immunol Immunother 2013;62(8):1421–1430.
  • Ko JS, Zea AH, Rini BI, Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res 2009;15(6):2148–2157.
  • Yuan X-K, Zhao X-K, Xia Y-C, Increased circulating immunosuppressive CD14(+)HLA-DR(−/low) cells correlate with clinical cancer stage and pathological grade in patients with bladder carcinoma. J Int Med Res 2011;39(4):1381–1391.
  • Vuk-Pavlovic S, Bulur PA, Lin Y, Immunosuppressive CD14+HLA-DRlow/- monocytes in prostate cancer. Prostate 2010;70(4):443–455.
  • Brusa D, Simone M, Gontero P, Circulating immunosuppressive cells of prostate cancer patients before and after radical prostatectomy: Profile comparison. Int J Urol 2013;20(10):971–978.
  • Mandruzzato S, Solito S, Falisi E, IL4Ralpha+ myeloid-derived suppressor cell expansion in cancer patients. J Immunol 2009;182(10):6562–6568.
  • Raychaudhuri B, Rayman P, Ireland J, Myeloid-derived suppressor cell accumulation and function in patients with newly diagnosed glioblastoma. Neuro Oncol 2011;13(6):591–599.
  • Gabitass RF, Annels NE, Stocken DD, Elevated myeloid-derived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13. Cancer Immunol Immunother 2011;60(10):1419–1430.
  • Annels NE, Shaw VE, Gabitass RF, The effects of gemcitabine and capecitabine combination chemotherapy and of low-dose adjuvant GM-CSF on the levels of myeloid-derived suppressor cells in patients with advanced pancreatic cancer. Cancer Immunol Immunother 2013;63(2):175–183.
  • Obermajer N, Muthuswamy R, Odunsi K, PGE2-induced CXCL12 production and CXCR4 expression controls the accumulation of human MDSCs in ovarian cancer environment. Cancer Res 2011;71(24):7463–7470.
  • Cui TX, Kryczek I, Zhao L, Myeloid-derived suppressor cells enhance stemness of cancer cells by inducing MicroRNA101 and suppressing the corepressor CtBP2. Immunity 2013;39(3):611–621.
  • Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 2011;11(11):723–737.
  • Rogers TL, Holen I. Tumour macrophages as potential targets of bisphosphonates. J Transl Med 2011;9(1):177.
  • Hao N-B, Lü M-H, Fan Y-H, Macrophages in tumor microenvironments and the progression of tumors. Clin Dev Immunol 2012;1–11.
  • Mantovani A, Sozzani S, Locati M, Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 2002;23(11):549–555.
  • Laoui D, Overmeire EV, Conza GD, Tumor hypoxia does not drive differentiation of tumor-associated macrophages but rather fine-tunes the M2-like macrophage population. Cancer Res 2014;74(1):24–30.
  • Noy R, Pollard JW. Tumor-associated macrophages: from mechanisms to therapy. Immunity 2014;41(1):49–61.
  • Sica A, Larghi P, Mancino A, Macrophage polarization in tumour progression. Semin Cancer Biol 2008;18(5):349–355.
  • Curiel TJ, Coukos G, Zou L, Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 2004;10(9):942–949.
  • Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments. Cancer Res 2006;66(2):605–612.
  • Colvin EK. Tumor-associated macrophages contribute to tumor progression in ovarian cancer. Front Oncol 2014;4:137.
  • Zhang BC, Gao J, Wang J, Tumor-associated macrophages infiltration is associated with peritumoral lymphangiogenesis and poor prognosis in lung adenocarcinoma. Med Oncol 2011;28(4):1447–1452.
  • Qian B-Z, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell 2010;141(1):39–51.
  • Bingle L, Brown NJ, Lewis CE. The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol 2002;196(3):254–265.
  • Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol 2010;11(10):889–896.
  • Takaishi K, Komohara Y, Tashiro H, Involvement of M2-polarized macrophages in the ascites from advanced epithelial ovarian carcinoma in tumor progression via Stat3 activation. Cancer Sci 2010;101(10):2128–2136.
  • Gordon IO, Freedman RS. Defective antitumor function of monocyte-derived macrophages from epithelial ovarian cancer patients. Clin Cancer Res 2006;12(5):1515–1524.
  • Klimp AH, Hollema H, Kempinga C, Expression of cyclooxygenase-2 and inducible nitric oxide synthase in human ovarian tumors and tumor-associated macrophages. Cancer Res 2001;61(19):7305–7309.
  • Wang X, Deavers M, Patenia R, Monocyte/macrophage and T-cell infiltrates in peritoneum of patients with ovarian cancer or benign pelvic disease. J Transl Med 2006;4:30.
  • Milne K, Köbel M, Kalloger SE, Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors. PLoS One 2009;4(7):e6412.
  • Shah CA, Allison KH, Garcia RL, Intratumoral T cells, tumor-associated macrophages, and regulatory T cells: association with p53 mutations, circulating tumor DNA and survival in women with ovarian cancer. Gynecol Oncol 2008;109(2):215–219.
  • Lan C, Huang X, Lin S, Expression of M2-polarized macrophages is associated with poor prognosis for advanced epithelial ovarian cancer. Technol Cancer Res Treat 2013;12(3):259–267.
  • No JH, Moon JM, Kim K, Prognostic significance of serum soluble CD163 level in patients with epithelial ovarian cancer. Gynecol Obstet Invest 2013;75(4):263–267.
  • Le Page C, Marineau A, Bonza PK, BTN3A2 Expression in epithelial ovarian cancer is associated with higher tumor infiltrating T cells and a better prognosis. PLoS One 2012;7(6):e38541.
  • Allavena P, Chieppa M, Bianchi G, Engagement of the mannose receptor by tumoralmucins activates an immune suppressive phenotype in human tumor-associated macrophages. Clin Dev Immunol 2010;2010:547179.
  • He Y, Zhang M, Wu X, et al. High MUC2 expression in ovarian cancer is inversely associated with the M1/M2 ratio of tumor-associated macrophages and patient survival time. PLoS One 2013;8(12):e79769.
  • Zhang M, He Y, Sun X, Li Q, Wang W, Zhao A, A high M1/M2 ratio of tumor-associated macrophages is associated with extended survival in ovarian cancer patients. J Ovarian Res 2014;7(1):19.
  • Wertel I, Surówka J, Polak G, Macrophage-derived chemokine CCL22 and regulatory T cells in ovarian cancer patients. Tumour Biol 2015; 36(6): 4811–4817.
  • Schutyser E, Struyf S, Proost P, Identification of biologically active chemokine isoforms from ascitic fluid and elevated levels of CCL18/pulmonary and activation-regulated chemokine in ovarian carcinoma. J BiolChem 2002;277(27):24584–24593.
  • Duluc D, Corvaisier M, Blanchard S, Interferon-gamma reverses the immunosuppressive and protumoral properties and prevents the generation of human tumor-associated macrophages. Int J Cancer 2009;125(2):367–373.
  • Leung J, Suh W-K. Host B7-H4 regulates antitumor T cell responses through inhibition of myeloid-derived suppressor cells in a 4T1 tumor transplantation model. J Immunol 2013;190(12):6651–6661.
  • Kryczek I, Wei S, Zhu G, Relationship between B7-H4, regulatory T cells, and patient outcome in human ovarian carcinoma. Cancer Res 2007;67(18):8900–8905.
  • Reinartz S, Schumann T, Finkernagel F, Mixed-polarization phenotype of ascites-associated macrophages in human ovarian carcinoma: correlation of CD163 expression, cytokine levels and early relapse. Int J Cancer 2014;134(1):32–42.
  • Biswas SK, Gangi L, Paul S, Schioppa T, Saccani A, Sironi M, A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-κB and enhanced IRF-3/STAT1 activation). Blood 2006;107(5):2112–2122.
  • Torroella-Kouri M, Silvera R, Identification of a subpopulation of macrophages in mammary tumor–bearing mice that are neither M1 nor M2 and are less differentiated. Cancer Res 2009;69(11):4800–4809.
  • Ojalvo LS, Whittaker CA, Condeelis JS, Gene expression analysis of macrophages that facilitate tumor invasion supports a role for Wnt-signaling in mediating their activity in primary mammary tumors. J Immunol 2010;184(2):702–712.
  • Ojalvo LS, King W, Cox D, High-density gene expression analysis of tumor-associated macrophages from mouse mammary tumors. Am J Pathol 2009;174(3):1048–1064.
  • Sica A, Bronte V. Altered macrophage differentiation and immune dysfunction in tumor development. J Clin Invest 2007;117(5):1155–1166.
  • Schumann T, Adhikary T, Wortmann A, Deregulation of PPARβ/δ target genes in tumor-associated macrophages by fatty acid ligands in the ovarian cancer microenvironment. Oncotarget 2015;6(15):13416–13433.
  • Wen Z, Liu H, Li M, Increased metabolites of 5-lipoxygenase from hypoxic ovarian cancer cells promote tumor-associated macrophage infiltration. Oncogene 2015;34(10):1241–1252.
  • Hagemann T, Robinson SC, Thompson RG, Ovarian cancer cell-derived migration inhibitory factor enhances tumor growth, progression, and angiogenesis. Mol Cancer Ther 2007;6(7):1993–2002.
  • Hagemann T, Lawrence T, McNeish I, “Re-educating” tumor-associated macrophages by targeting NF-κB. J Exp Med 2008;205(6):1261–1268.
  • Wang X, Zhao X, Wang K, Interaction of monocytes/macrophages with ovarian cancer cells promotes angiogenesis in vitro. Cancer Sci 2013;104(4):516–523.
  • Gabrilovich DI, Nagaraj S. Myeloid-derived-suppressor cells as regulators of the immune system. Nat Rev Immunol 2009;9(3):162–174.
  • Schouppe E, De Baetselier P, Van Ginderachter JA, Instruction of myeloid cells by the tumor microenvironment. Oncoimmunology 2012;1(7):1135–1145.
  • Youn J-I, Gabrilovich DI. The biology of myeloid-derived suppressor cells: The blessing and the curse of morphological and functional heterogeneity. Eur J Immunol 2010;40(11):2969–2975.
  • Trikha P, Carson III WE. Signaling pathways involved in MDSC regulation. Biochim Biophys Acta 2014;1846(1):55–65.
  • Sinha P, Clements VK, Bunt SK, Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J Immunol 2007;179(2):977–983.
  • Rodriguez PC, Hernandez CP, Quiceno D, Arginase I in myeloid suppressor cells is induced by COX-2 in lung carcinoma. J Exp Med 2005;202(7):931–939.
  • Pan P-Y, Wang GX, Yin B, Reversion of immune tolerance in advanced malignancy: modulation of myeloid-derived suppressor cell development by blockade of stem-cell factor function. Blood 2008;111(1):219–228.
  • Kusmartsev S, Cheng F, Yu B, All-trans-retinoic acid eliminates immature myeloid cells from tumor-bearing mice and improves the effect of vaccination. Cancer Res 2003;63(15):4441–4449.
  • Mace TA, Ameen Z, Collins A, Pancreatic cancer-associated stellate cells promote differentiation of myeloid-derived suppressor cells in a STAT3-dependent manner. Cancer Res 2013;73:3007–3018.
  • Serafini P, Carbley R, Noonan KA, High-dose granulocyte-macrophage colony-stimulating factor-producing vaccines impair the immune response through the recruitment of myeloid suppressor cells. Cancer Res 2004;64(17):6337–6343.
  • Gabrilovich D, Ishida T, Oyama T, Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood 1998;92(11):4150–4166.
  • Gallina G, Dolcetti L, Serafini P, Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells. J Clin Invest 2006;116(10):2777–2790.
  • Zea AH, Rodriguez PC, Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion. Cancer Res 2005;65(8):3044–3048.
  • Bronte V, Serafini P, De Santo C, IL-4-induced arginase 1 suppresses alloreactive T cells in tumor-bearing mice. J Immunol 2003;170(1):270–278.
  • Terabe M, Matsui S, Park J-M, Transforming growth factor-β production and myeloid cells are an effector mechanism through which CD1d-restricted T cells block cytotoxic T lymphocyte–mediated tumor immunosurveillance abrogation prevents tumor recurrence. J Exp Med 2003;198(11):1741–1752.
  • Yang L, Huang J, Ren X, Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis. Cancer Cell 2008;13(1):23–35.
  • Lindau D, Gielen P, Kroesen M, The immunosuppressive tumour network: myeloid-derived suppressor cells, regulatory T cells and natural killer T cells. Immunology 2013;138(2):105–115.
  • Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 2012;12(4):253–268.
  • Kryczek I, Lange A, Mottram P, CXCL12 and vascular endothelial growth factor synergistically induce neoangiogenesis in human ovarian cancers. Cancer Res 2005;65(2):465–472.
  • Zou W, Machelon V, Coulomb-L’Hermin A, Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells. Nat Med 2001;7(12):1339–1346.
  • Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 2006;6(4):295–307.
  • Serafini P. Editorial: PGE2-producing MDSC: a role in tumor progression? J Leukoc Biol 2010;88(5):827–829.
  • Diaz-Montero CM, Finke J, Montero AJ. Myeloid-derived suppressor cells in cancer: therapeutic, predictive, and prognostic implications. Semin Oncol 2014;41(2):174–184.
  • Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 2004;4(1):71–78.
  • Damuzzo V, Pinton L, Desantis G, Complexity and challenges in defining myeloid-derived suppressor cells. Cytometry B Clin Cytom 2015;88(2):77–91.
  • Kotsakis A, Harasymczuk M, Schilling B, Myeloid-derived suppressor cell measurements in fresh and cryopreserved blood samples. J Immunol Methods 2012;381(1-2):14–22.

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