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Published in: Cancer Microenvironment 2/2013

01-08-2013 | Original Paper

Tumor Microenvironment and Myeloid-Derived Suppressor Cells

Authors: Viktor Umansky, Alexandra Sevko

Published in: Cancer Microenvironment | Issue 2/2013

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Abstract

Tumor progression has been demonstrated to be supported by chronic inflammatory conditions developed in the tumor microenvironment and characterized by the long-term secretion of various inflammatory soluble factors (including cytokines, chemokines, growth factors, reactive oxygen and nitrogen species, prostaglandins etc.) and strong leukocyte infiltration. Among leukocytes infiltrating tumors, myeloid-derived suppressor cells (MDSCs) represent one of the most important players mediating immunosuppression. These cells may not only strongly inhibit an anti-tumor immune reactions mediated by T cells but also directly stimulate tumorigenesis, tumor growth and metastasis by enhancing neoangiogenesis and creating a suitable environment for the metastatic formation. This review provides an overview of interactions between MDSCs and tumor cells leading to MDSC generation, activation and migration to the tumor site, where they can strongly enhance tumor progression. Better understanding of the MDSC-tumor interplay is critical for the development of new strategies of tumor immunotherapy.
Literature
1.
go back to reference Ramirez-Montagut T, Turk MJ, Wolchok JD et al (2003) Immunity to melanoma: unraveling the relation of tumor immunity and autoimmunity. Oncogene 22:3180–3187PubMedCrossRef Ramirez-Montagut T, Turk MJ, Wolchok JD et al (2003) Immunity to melanoma: unraveling the relation of tumor immunity and autoimmunity. Oncogene 22:3180–3187PubMedCrossRef
2.
go back to reference Driessens G, Kline J, Gajewski TF (2009) Costimulatory and coinhibitory receptors in anti-tumor immunity. Immunol Rev 229:126–144PubMedCrossRef Driessens G, Kline J, Gajewski TF (2009) Costimulatory and coinhibitory receptors in anti-tumor immunity. Immunol Rev 229:126–144PubMedCrossRef
3.
go back to reference Fridman WH, Pagès F, Sautès-Fridman C et al (2012) The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer 12:298–306PubMedCrossRef Fridman WH, Pagès F, Sautès-Fridman C et al (2012) The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer 12:298–306PubMedCrossRef
4.
go back to reference Mlecnik B, Bindea G, Pagès F et al (2011) Tumor immunosurveillance in human cancers. Cancer Metastasis Rev 30:5–12PubMedCrossRef Mlecnik B, Bindea G, Pagès F et al (2011) Tumor immunosurveillance in human cancers. Cancer Metastasis Rev 30:5–12PubMedCrossRef
5.
go back to reference Gooden MJ, de Bock GH, Leffers N et al (2011) The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis. Br J Cancer 105:93–103PubMedCrossRef Gooden MJ, de Bock GH, Leffers N et al (2011) The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis. Br J Cancer 105:93–103PubMedCrossRef
6.
go back to reference Klebanoff CA, Acquavella N, Yu Z et al (2011) Therapeutic cancer vaccines: are we there yet? Immunol Rev 239:27–44PubMedCrossRef Klebanoff CA, Acquavella N, Yu Z et al (2011) Therapeutic cancer vaccines: are we there yet? Immunol Rev 239:27–44PubMedCrossRef
7.
go back to reference van der Bruggen P, Van den Eynde BJ (2006) Processing and presentation of tumor antigens and vaccination strategies. Curr Opin Immunol 18:98–104PubMedCrossRef van der Bruggen P, Van den Eynde BJ (2006) Processing and presentation of tumor antigens and vaccination strategies. Curr Opin Immunol 18:98–104PubMedCrossRef
8.
go back to reference Rosenberg SA (2011) Cell transfer immunotherapy for metastatic solid cancer–what clinicians need to know. Nat Rev Clin Oncol 8:577–585PubMedCrossRef Rosenberg SA (2011) Cell transfer immunotherapy for metastatic solid cancer–what clinicians need to know. Nat Rev Clin Oncol 8:577–585PubMedCrossRef
9.
go back to reference Ferrone S, Marincola FM (1995) Loss of HLA class I antigens by melanoma cells: molecular mechanisms, functional significance and clinical relevance. Immunol Today 16:487–494PubMedCrossRef Ferrone S, Marincola FM (1995) Loss of HLA class I antigens by melanoma cells: molecular mechanisms, functional significance and clinical relevance. Immunol Today 16:487–494PubMedCrossRef
10.
go back to reference Garrido F, Algarra I, García-Lora AM (2010) The escape of cancer from T lymphocytes: immunoselection of MHC class I loss variants harboring structural-irreversible “hard” lesions. Cancer Immunol Immunother 59:1601–1606PubMedCrossRef Garrido F, Algarra I, García-Lora AM (2010) The escape of cancer from T lymphocytes: immunoselection of MHC class I loss variants harboring structural-irreversible “hard” lesions. Cancer Immunol Immunother 59:1601–1606PubMedCrossRef
11.
go back to reference Seliger B (2012) Novel insights into the molecular mechanisms of HLA class I abnormalities. Cancer Immunol Immunother 61:249–254PubMedCrossRef Seliger B (2012) Novel insights into the molecular mechanisms of HLA class I abnormalities. Cancer Immunol Immunother 61:249–254PubMedCrossRef
12.
go back to reference Rivoltini L, Canese P, Huber V et al (2005) Escape strategies and reasons for failure in the interaction between tumour cells and the immune system: how can we tilt the balance towards immune-mediated cancer control? Expert Opin Biol Ther 5:463–476PubMedCrossRef Rivoltini L, Canese P, Huber V et al (2005) Escape strategies and reasons for failure in the interaction between tumour cells and the immune system: how can we tilt the balance towards immune-mediated cancer control? Expert Opin Biol Ther 5:463–476PubMedCrossRef
13.
go back to reference Kusmartsev S, Gabrilovich DI (2006) Effect of tumor-derived cytokines and growth factors on differentiation and immune suppressive features of myeloid cells in cancer. Cancer Metastasis Rev 25:323–331PubMedCrossRef Kusmartsev S, Gabrilovich DI (2006) Effect of tumor-derived cytokines and growth factors on differentiation and immune suppressive features of myeloid cells in cancer. Cancer Metastasis Rev 25:323–331PubMedCrossRef
14.
go back to reference Ostrand-Rosenberg S (2008) Immune surveillance: a balance between protumor and antitumor immunity. Curr Opin Genet Dev 18:11–18PubMedCrossRef Ostrand-Rosenberg S (2008) Immune surveillance: a balance between protumor and antitumor immunity. Curr Opin Genet Dev 18:11–18PubMedCrossRef
15.
go back to reference Gajewski TF (2007) Failure at the effector phase: immune barriers at the level of the melanoma tumor microenvironment. Clin Cancer Res 13:5256–5261PubMedCrossRef Gajewski TF (2007) Failure at the effector phase: immune barriers at the level of the melanoma tumor microenvironment. Clin Cancer Res 13:5256–5261PubMedCrossRef
16.
go back to reference Nishikawa H, Sakaguchi S (2010) Regulatory T cells in tumor immunity. Int J Cancer 127:759–767PubMed Nishikawa H, Sakaguchi S (2010) Regulatory T cells in tumor immunity. Int J Cancer 127:759–767PubMed
17.
go back to reference Sica A, Larghi P, Mancino A et al (2008) Macrophage polarization in tumour progression. Semin Cancer Biol 18:349–355PubMedCrossRef Sica A, Larghi P, Mancino A et al (2008) Macrophage polarization in tumour progression. Semin Cancer Biol 18:349–355PubMedCrossRef
18.
go back to reference Lewis CE, De Palma M, Naldini L (2007) Tie2-expressing monocytes and tumor angiogenesis: regulation by hypoxia and angiopoietin-2. Cancer Res 67:8429–8432PubMedCrossRef Lewis CE, De Palma M, Naldini L (2007) Tie2-expressing monocytes and tumor angiogenesis: regulation by hypoxia and angiopoietin-2. Cancer Res 67:8429–8432PubMedCrossRef
19.
go back to reference Fridlender ZG, Sun J, Kim S et al (2009) Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell 16:183–194PubMedCrossRef Fridlender ZG, Sun J, Kim S et al (2009) Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell 16:183–194PubMedCrossRef
20.
go back to reference Shurin MR, Naiditch H, Zhong H, Shurin GV (2011) Regulatory dendritic cells: new targets for cancer immunotherapy. Cancer Biol Ther 11:988–992PubMedCrossRef Shurin MR, Naiditch H, Zhong H, Shurin GV (2011) Regulatory dendritic cells: new targets for cancer immunotherapy. Cancer Biol Ther 11:988–992PubMedCrossRef
21.
go back to reference Gabrilovich DI, Ostrand-Rosenberg S, Bronte V (2012) Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 12:253–268PubMedCrossRef Gabrilovich DI, Ostrand-Rosenberg S, Bronte V (2012) Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 12:253–268PubMedCrossRef
22.
go back to reference Ostrand-Rosenberg S (2010) Myeloid-derived suppressor cells: more mechanisms for inhibiting antitumor immunity. Cancer Immunol Immunother 59:1593–1600PubMedCrossRef Ostrand-Rosenberg S (2010) Myeloid-derived suppressor cells: more mechanisms for inhibiting antitumor immunity. Cancer Immunol Immunother 59:1593–1600PubMedCrossRef
23.
go back to reference Young PP, Ardestani S, Li B (2010) Myeloid cells in cancer progression: unique subtypes and their roles in tumor growth, vascularity, and host immune suppression. Cancer Microenviron 4:1–11PubMedCrossRef Young PP, Ardestani S, Li B (2010) Myeloid cells in cancer progression: unique subtypes and their roles in tumor growth, vascularity, and host immune suppression. Cancer Microenviron 4:1–11PubMedCrossRef
24.
go back to reference Ostrand-Rosenberg S, Sinha P (2009) Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol 182:4499–4506PubMedCrossRef Ostrand-Rosenberg S, Sinha P (2009) Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol 182:4499–4506PubMedCrossRef
25.
go back to reference Baniyash M (2006) Chronic inflammation, immunosuppression and cancer: new insights and outlook. Semin Cancer Biol 16:80–88PubMedCrossRef Baniyash M (2006) Chronic inflammation, immunosuppression and cancer: new insights and outlook. Semin Cancer Biol 16:80–88PubMedCrossRef
26.
go back to reference Condamine T, Gabrilovich DI (2011) Molecular mechanisms regulating myeloid-derived suppressor cell differentiation and function. Trends Immunol 32:19–25PubMedCrossRef Condamine T, Gabrilovich DI (2011) Molecular mechanisms regulating myeloid-derived suppressor cell differentiation and function. Trends Immunol 32:19–25PubMedCrossRef
27.
go back to reference Marigo I, Dolcetti L, Serafini P et al (2008) Tumor-induced tolerance and immune suppression by myeloid derived suppressor cells. Immunol Rev 222:162–179PubMedCrossRef Marigo I, Dolcetti L, Serafini P et al (2008) Tumor-induced tolerance and immune suppression by myeloid derived suppressor cells. Immunol Rev 222:162–179PubMedCrossRef
28.
go back to reference Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9:162–174PubMedCrossRef Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9:162–174PubMedCrossRef
29.
go back to reference Youn JI, Gabrilovich DI (2010) The biology of myeloid-derived suppressor cells: the blessing and the curse of morphological and functional heterogeneity. Eur J Immunol 40:2969–2975PubMedCrossRef Youn JI, Gabrilovich DI (2010) The biology of myeloid-derived suppressor cells: the blessing and the curse of morphological and functional heterogeneity. Eur J Immunol 40:2969–2975PubMedCrossRef
30.
go back to reference Montero AJ, Diaz-Montero CM, Kyriakopoulos CE et al (2012) Myeloid-derived suppressor cells in cancer patients: a clinical perspective. J Immunother 35:107–115PubMedCrossRef Montero AJ, Diaz-Montero CM, Kyriakopoulos CE et al (2012) Myeloid-derived suppressor cells in cancer patients: a clinical perspective. J Immunother 35:107–115PubMedCrossRef
31.
go back to reference Filipazzi P, Huber V, Rivoltini L (2012) Phenotype, function and clinical implications of myeloid-derived suppressor cells in cancer patients. Cancer Immunol Immunother 61:255–263PubMedCrossRef Filipazzi P, Huber V, Rivoltini L (2012) Phenotype, function and clinical implications of myeloid-derived suppressor cells in cancer patients. Cancer Immunol Immunother 61:255–263PubMedCrossRef
32.
go back to reference Wu L, Yan C, Czader M et al (2012) Inhibition of PPARγ in myeloid-lineage cells induces systemic inflammation, immunosuppression, and tumorigenesis. Blood 119:115–126PubMedCrossRef Wu L, Yan C, Czader M et al (2012) Inhibition of PPARγ in myeloid-lineage cells induces systemic inflammation, immunosuppression, and tumorigenesis. Blood 119:115–126PubMedCrossRef
33.
go back to reference Sonda N, Chioda M, Zilio S et al (2011) Transcription factors in myeloid-derived suppressor cell recruitment and function. Curr Opin Immunol 23:279–285PubMedCrossRef Sonda N, Chioda M, Zilio S et al (2011) Transcription factors in myeloid-derived suppressor cell recruitment and function. Curr Opin Immunol 23:279–285PubMedCrossRef
35.
go back to reference Molon B, Ugel S, Del Pozzo F (2011) Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells. J Exp Med 208:1949–1962PubMedCrossRef Molon B, Ugel S, Del Pozzo F (2011) Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells. J Exp Med 208:1949–1962PubMedCrossRef
36.
go back to reference Li H, Han Y, Guo Q et al (2009) Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-beta 1. J Immunol 182:240–249PubMed Li H, Han Y, Guo Q et al (2009) Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-beta 1. J Immunol 182:240–249PubMed
37.
go back to reference Bronte V, Zanovello P (2005) Regulation of immune responses by L-arginine metabolism. Nat Rev Immunol 5:641–654PubMedCrossRef Bronte V, Zanovello P (2005) Regulation of immune responses by L-arginine metabolism. Nat Rev Immunol 5:641–654PubMedCrossRef
38.
go back to reference Rodríguez PC, Ochoa AC (2006) T cell dysfunction in cancer: role of myeloid cells and tumor cells regulating amino acid availability and oxidative stress. Semin Cancer Biol 16:66–72PubMedCrossRef Rodríguez PC, Ochoa AC (2006) T cell dysfunction in cancer: role of myeloid cells and tumor cells regulating amino acid availability and oxidative stress. Semin Cancer Biol 16:66–72PubMedCrossRef
39.
go back to reference Srivastava MK, Sinha P, Clements VK et al (2010) Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine. Cancer Res 70:68–77PubMedCrossRef Srivastava MK, Sinha P, Clements VK et al (2010) Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine. Cancer Res 70:68–77PubMedCrossRef
40.
go back to reference Hanson EM, Clements VK, Sinha P et al (2009) Myeloid-derived suppressor cells down-regulate L-selectin expression on CD4+ and CD8+ T cells. J Immunol 183:937–944PubMedCrossRef Hanson EM, Clements VK, Sinha P et al (2009) Myeloid-derived suppressor cells down-regulate L-selectin expression on CD4+ and CD8+ T cells. J Immunol 183:937–944PubMedCrossRef
41.
go back to reference Ezernitchi AV, Vaknin I, Cohen-Daniel L et al (2006) TCR zeta down-regulation under chronic inflammation is mediated by myeloid suppressor cells differentially distributed between various lymphatic organs. J Immunol 177:4763–4772PubMed Ezernitchi AV, Vaknin I, Cohen-Daniel L et al (2006) TCR zeta down-regulation under chronic inflammation is mediated by myeloid suppressor cells differentially distributed between various lymphatic organs. J Immunol 177:4763–4772PubMed
42.
go back to reference Rodríguez PC, Zea AH, Culotta KS et al (2002) Regulation of T cell receptor CD3zeta chain expression by L-arginine. J Biol Chem 277:21123–21129PubMedCrossRef Rodríguez PC, Zea AH, Culotta KS et al (2002) Regulation of T cell receptor CD3zeta chain expression by L-arginine. J Biol Chem 277:21123–21129PubMedCrossRef
43.
go back to reference Sebens Müerköster S, Werbing V, Sipos B et al (2007) Drug-induced expression of the cellular adhesion molecule L1CAM confers anti-apoptotic protection and chemoresistance in pancreatic ductal adenocarcinoma cells. Oncogene 26:2759–2768PubMedCrossRef Sebens Müerköster S, Werbing V, Sipos B et al (2007) Drug-induced expression of the cellular adhesion molecule L1CAM confers anti-apoptotic protection and chemoresistance in pancreatic ductal adenocarcinoma cells. Oncogene 26:2759–2768PubMedCrossRef
44.
go back to reference Tartour E, Pere H, Maillere B et al (2011) Angiogenesis and immunity: a bidirectional link potentially relevant for the monitoring of antiangiogenic therapy and the development of novel therapeutic combination with immunotherapy. Cancer Metastasis Rev 30:83–95PubMedCrossRef Tartour E, Pere H, Maillere B et al (2011) Angiogenesis and immunity: a bidirectional link potentially relevant for the monitoring of antiangiogenic therapy and the development of novel therapeutic combination with immunotherapy. Cancer Metastasis Rev 30:83–95PubMedCrossRef
45.
go back to reference Serafini P, Mgebroff S, Noonan K et al (2008) Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells. Cancer Res 68:5439–5449PubMedCrossRef Serafini P, Mgebroff S, Noonan K et al (2008) Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells. Cancer Res 68:5439–5449PubMedCrossRef
46.
go back to reference Qu P, Yan C, Du H (2011) Matrix metalloproteinase 12 overexpression in myeloid lineage cells plays a key role in modulating myelopoiesis, immune suppression, and lung tumorigenesis. Blood 117:4476–4489PubMedCrossRef Qu P, Yan C, Du H (2011) Matrix metalloproteinase 12 overexpression in myeloid lineage cells plays a key role in modulating myelopoiesis, immune suppression, and lung tumorigenesis. Blood 117:4476–4489PubMedCrossRef
47.
go back to reference Sevko A, Sade-Feldman M, Kanterman J et al. (2012) Cyclophosphamide promotes chronic inflammation-dependent immunosuppression and prevents anti-tumor response in melanoma. J Invest Dermatol, in press Sevko A, Sade-Feldman M, Kanterman J et al. (2012) Cyclophosphamide promotes chronic inflammation-dependent immunosuppression and prevents anti-tumor response in melanoma. J Invest Dermatol, in press
48.
go back to reference Meyer C, Sevko A, Ramacher M et al (2011) Chronic inflammation promotes myeloid-derived suppressor cell activation blocking antitumor immunity in transgenic mouse melanoma model. Proc Natl Acad Sci U S A 108:17111–17116PubMedCrossRef Meyer C, Sevko A, Ramacher M et al (2011) Chronic inflammation promotes myeloid-derived suppressor cell activation blocking antitumor immunity in transgenic mouse melanoma model. Proc Natl Acad Sci U S A 108:17111–17116PubMedCrossRef
49.
go back to reference Bunt SK, Yang L, Sinha P et al (2007) Reduced inflammation in the tumor microenvironment delays the accumulation of myeloid-derived suppressor cells and limits tumor progression. Cancer Res 67:10019–10026PubMedCrossRef Bunt SK, Yang L, Sinha P et al (2007) Reduced inflammation in the tumor microenvironment delays the accumulation of myeloid-derived suppressor cells and limits tumor progression. Cancer Res 67:10019–10026PubMedCrossRef
50.
go back to reference Haverkamp JM, Crist SA, Elzey BD et al (2011) In vivo suppressive function of myeloid-derived suppressor cells is limited to the inflammatory site. Eur J Immunol 41:749–759PubMedCrossRef Haverkamp JM, Crist SA, Elzey BD et al (2011) In vivo suppressive function of myeloid-derived suppressor cells is limited to the inflammatory site. Eur J Immunol 41:749–759PubMedCrossRef
51.
go back to reference Mikyšková R, Indrová M, Polláková V et al (2012) Cyclophosphamide-induced myeloid-derived suppressor cell population is immunosuppressive but not identical to myeloid-derived suppressor cells induced by growing TC-1 tumors. J Immunother 35:374–384PubMedCrossRef Mikyšková R, Indrová M, Polláková V et al (2012) Cyclophosphamide-induced myeloid-derived suppressor cell population is immunosuppressive but not identical to myeloid-derived suppressor cells induced by growing TC-1 tumors. J Immunother 35:374–384PubMedCrossRef
52.
go back to reference Chornoguz O, Grmai L, Sinha P (2011) Proteomic pathway analysis reveals inflammation increases myeloid-derived suppressor cell resistance to apoptosis. Mol Cell Proteomics 10:M110.002980PubMedCrossRef Chornoguz O, Grmai L, Sinha P (2011) Proteomic pathway analysis reveals inflammation increases myeloid-derived suppressor cell resistance to apoptosis. Mol Cell Proteomics 10:M110.002980PubMedCrossRef
53.
go back to reference Filipazzi P, Bürdek M, Villa A et al (2012) Recent advances on the role of tumor exosomes in immunosuppression and disease progression. Semin Cancer Biol 22:342–349PubMedCrossRef Filipazzi P, Bürdek M, Villa A et al (2012) Recent advances on the role of tumor exosomes in immunosuppression and disease progression. Semin Cancer Biol 22:342–349PubMedCrossRef
54.
go back to reference Taylor DD, Gercel-Taylor C (2011) Exosomes/microvesicles: mediators of cancer-associated immunosuppressive microenvironments. Semin Immunopathol 33:441–454PubMedCrossRef Taylor DD, Gercel-Taylor C (2011) Exosomes/microvesicles: mediators of cancer-associated immunosuppressive microenvironments. Semin Immunopathol 33:441–454PubMedCrossRef
55.
go back to reference Barreda DR, Hanington PC, Belosevic M (2004) Regulation of myeloid development and function by colony stimulating factors. Dev Comp Immunol 28:509–554PubMedCrossRef Barreda DR, Hanington PC, Belosevic M (2004) Regulation of myeloid development and function by colony stimulating factors. Dev Comp Immunol 28:509–554PubMedCrossRef
56.
go back to reference Maione P, Rossi A, Di Maio M et al (2009) Tumor-related leucocytosis and chemotherapy-induced neutropenia: linked or independent prognostic factors for advanced non-small cell lung cancer? Lung Cancer 66:8–14PubMedCrossRef Maione P, Rossi A, Di Maio M et al (2009) Tumor-related leucocytosis and chemotherapy-induced neutropenia: linked or independent prognostic factors for advanced non-small cell lung cancer? Lung Cancer 66:8–14PubMedCrossRef
57.
go back to reference Revoltella RP, Menicagli M, Campani D (2012) Granulocyte-macrophage colony-stimulating factor as an autocrine survival-growth factor in human gliomas. Cytokine 57:347–359PubMedCrossRef Revoltella RP, Menicagli M, Campani D (2012) Granulocyte-macrophage colony-stimulating factor as an autocrine survival-growth factor in human gliomas. Cytokine 57:347–359PubMedCrossRef
58.
go back to reference Dolcetti L, Peranzoni E, Ugel S et al (2010) Hierarchy of immunosuppressive strength among myeloid-derived suppressor cell subsets is determined by GM-CSF. Eur J Immunol 40:22–35PubMedCrossRef Dolcetti L, Peranzoni E, Ugel S et al (2010) Hierarchy of immunosuppressive strength among myeloid-derived suppressor cell subsets is determined by GM-CSF. Eur J Immunol 40:22–35PubMedCrossRef
59.
go back to reference Ribechini E, Greifenberg V, Sandwick S et al (2010) Subsets, expansion and activation of myeloid-derived suppressor cells. Med Microbiol Immunol 199:273–281PubMedCrossRef Ribechini E, Greifenberg V, Sandwick S et al (2010) Subsets, expansion and activation of myeloid-derived suppressor cells. Med Microbiol Immunol 199:273–281PubMedCrossRef
60.
go back to reference Lechner MG, Liebertz DJ, Epstein AL (2010) Characterization of cytokine-induced myeloid-derived suppressor cells from normal human peripheral blood mononuclear cells. J Immunol 185:2273–2284PubMedCrossRef Lechner MG, Liebertz DJ, Epstein AL (2010) Characterization of cytokine-induced myeloid-derived suppressor cells from normal human peripheral blood mononuclear cells. J Immunol 185:2273–2284PubMedCrossRef
61.
go back to reference Casella I, Feccia T, Chelucci C et al (2003) Autocrine-paracrine VEGF loops potentiate the maturation of megakaryocytic precursors through Flt1 receptor. Blood 101:1316–1323PubMedCrossRef Casella I, Feccia T, Chelucci C et al (2003) Autocrine-paracrine VEGF loops potentiate the maturation of megakaryocytic precursors through Flt1 receptor. Blood 101:1316–1323PubMedCrossRef
62.
go back to reference Söderberg SS, Karlsson G, Karlsson S (2009) Complex and context dependent regulation of hematopoiesis by TGF-beta superfamily signaling. Ann N Y Acad Sci 1176:55–69PubMedCrossRef Söderberg SS, Karlsson G, Karlsson S (2009) Complex and context dependent regulation of hematopoiesis by TGF-beta superfamily signaling. Ann N Y Acad Sci 1176:55–69PubMedCrossRef
63.
go back to reference Johnson B, Osada T, Clay T et al (2009) Physiology and therapeutics of vascular endothelial growth factor in tumor immunosuppression. Curr Mol Med 9:702–707PubMedCrossRef Johnson B, Osada T, Clay T et al (2009) Physiology and therapeutics of vascular endothelial growth factor in tumor immunosuppression. Curr Mol Med 9:702–707PubMedCrossRef
64.
go back to reference 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 22:275–281PubMedCrossRef 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 22:275–281PubMedCrossRef
65.
go back to reference Flavell RA, Sanjabi S, Wrzesinski SH et al (2010) The polarization of immune cells in the tumour environment by TGFbeta. Nat Rev Immunol 10:554–567PubMedCrossRef Flavell RA, Sanjabi S, Wrzesinski SH et al (2010) The polarization of immune cells in the tumour environment by TGFbeta. Nat Rev Immunol 10:554–567PubMedCrossRef
66.
go back to reference Apte RN, Voronov E (2008) Is interleukin-1 a good or bad ‘guy’ in tumor immunobiology and immunotherapy? Immunol Rev 222:222–241PubMedCrossRef Apte RN, Voronov E (2008) Is interleukin-1 a good or bad ‘guy’ in tumor immunobiology and immunotherapy? Immunol Rev 222:222–241PubMedCrossRef
67.
go back to reference Elkabets M, Ribeiro VS, Dinarello CA et al (2010) IL-1β regulates a novel myeloid-derived suppressor cell subset that impairs NK cell development and function. Eur J Immunol 40:3347–3357PubMedCrossRef Elkabets M, Ribeiro VS, Dinarello CA et al (2010) IL-1β regulates a novel myeloid-derived suppressor cell subset that impairs NK cell development and function. Eur J Immunol 40:3347–3357PubMedCrossRef
68.
go back to reference Tu S, Bhagat G, Cui G et al (2008) Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer Cell 14:408–419PubMedCrossRef Tu S, Bhagat G, Cui G et al (2008) Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer Cell 14:408–419PubMedCrossRef
69.
go back to reference Sinha P, Clements VK, Fulton AM et al (2007) Prostaglandin E2 promotes tumor progression by inducing myeloid-derived suppressor cells. Cancer Res 67:4507–4513PubMedCrossRef Sinha P, Clements VK, Fulton AM et al (2007) Prostaglandin E2 promotes tumor progression by inducing myeloid-derived suppressor cells. Cancer Res 67:4507–4513PubMedCrossRef
70.
go back to reference Eruslanov E, Daurkin I, Ortiz J et al (2010) Pivotal advance: tumor-mediated induction of myeloid-derived suppressor cells and M2-polarized macrophages by altering intracellular PGE2 catabolism in myeloid cells. J Leukoc Biol 88:39–48CrossRef Eruslanov E, Daurkin I, Ortiz J et al (2010) Pivotal advance: tumor-mediated induction of myeloid-derived suppressor cells and M2-polarized macrophages by altering intracellular PGE2 catabolism in myeloid cells. J Leukoc Biol 88:39–48CrossRef
71.
go back to reference Ledesma E, Martνnez I, Cσrdova Y et al (2004) Interleukin-1 beta (IL-1beta) induces tumor necrosis factor alpha (TNF-alpha) expression on mouse myeloid multipotent cell line 32D cl3 and inhibits their proliferation. Cytokine 26:66–72PubMedCrossRef Ledesma E, Martνnez I, Cσrdova Y et al (2004) Interleukin-1 beta (IL-1beta) induces tumor necrosis factor alpha (TNF-alpha) expression on mouse myeloid multipotent cell line 32D cl3 and inhibits their proliferation. Cytokine 26:66–72PubMedCrossRef
72.
go back to reference Park EJ, Kwon TK (2011) Rottlerin enhances IL-1β-induced COX-2 expression through sustained p38 MAPK activation in MDA-MB-231 human breast cancer cells. Exp Mol Med 43:669–675PubMedCrossRef Park EJ, Kwon TK (2011) Rottlerin enhances IL-1β-induced COX-2 expression through sustained p38 MAPK activation in MDA-MB-231 human breast cancer cells. Exp Mol Med 43:669–675PubMedCrossRef
73.
go back to reference Bunt SK, Clements VK, Hanson EM et al (2009) Inflammation enhances myeloid-derived suppressor cell cross-talk by signaling through Toll-like receptor 4. J Leukoc Biol 85:996–1004PubMedCrossRef Bunt SK, Clements VK, Hanson EM et al (2009) Inflammation enhances myeloid-derived suppressor cell cross-talk by signaling through Toll-like receptor 4. J Leukoc Biol 85:996–1004PubMedCrossRef
74.
go back to reference Gabitass RF, Annels NE, Stocken DD et al (2011) 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 60:1419–1430PubMedCrossRef Gabitass RF, Annels NE, Stocken DD et al (2011) 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 60:1419–1430PubMedCrossRef
75.
go back to reference Carmi Y, Voronov E, Dotan S (2009) The role of macrophage-derived IL-1 in induction and maintenance of angiogenesis. J Immunol 183:4705–4714PubMedCrossRef Carmi Y, Voronov E, Dotan S (2009) The role of macrophage-derived IL-1 in induction and maintenance of angiogenesis. J Immunol 183:4705–4714PubMedCrossRef
76.
go back to reference Greifenberg V, Ribechini E, Rössner S et al (2009) Myeloid-derived suppressor cell activation by combined LPS and IFN-gamma treatment impairs DC development. Eur J Immunol 39:2865–2876PubMedCrossRef Greifenberg V, Ribechini E, Rössner S et al (2009) Myeloid-derived suppressor cell activation by combined LPS and IFN-gamma treatment impairs DC development. Eur J Immunol 39:2865–2876PubMedCrossRef
77.
go back to reference Neurath MF, Finotto S (2011) IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated cancer. Cytokine Growth Factor Rev 22:83–89PubMedCrossRef Neurath MF, Finotto S (2011) IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated cancer. Cytokine Growth Factor Rev 22:83–89PubMedCrossRef
78.
go back to reference Mundy-Bosse BL, Young GS, Bauer T et al (2011) Distinct myeloid suppressor cell subsets correlate with plasma IL-6 and IL-10 and reduced interferon-alpha signaling in CD4 T cells from patients with GI malignancy. Cancer Immunol Immunother 60:1269–1279PubMedCrossRef Mundy-Bosse BL, Young GS, Bauer T et al (2011) Distinct myeloid suppressor cell subsets correlate with plasma IL-6 and IL-10 and reduced interferon-alpha signaling in CD4 T cells from patients with GI malignancy. Cancer Immunol Immunother 60:1269–1279PubMedCrossRef
79.
go back to reference Chalmin F, Ladoire S, Mignot G et al (2010) Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. J Clin Invest 120:457–471PubMed Chalmin F, Ladoire S, Mignot G et al (2010) Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. J Clin Invest 120:457–471PubMed
80.
go back to reference Sumida K, Wakita D, Narita Y et al (2012) Anti-IL-6 receptor mAb eliminates myeloid-derived suppressor cells and inhibits tumor growth by enhancing T-cell responses. Eur J Immunol 42:2060–2072PubMedCrossRef Sumida K, Wakita D, Narita Y et al (2012) Anti-IL-6 receptor mAb eliminates myeloid-derived suppressor cells and inhibits tumor growth by enhancing T-cell responses. Eur J Immunol 42:2060–2072PubMedCrossRef
81.
go back to reference Lesokhin AM, Hohl TM, Kitano S et al (2012) Monocytic CCR2(+) myeloid-derived suppressor cells promote immune escape by limiting activated CD8 T-cell infiltration into the tumor microenvironment. Cancer Res 72:876–886PubMedCrossRef Lesokhin AM, Hohl TM, Kitano S et al (2012) Monocytic CCR2(+) myeloid-derived suppressor cells promote immune escape by limiting activated CD8 T-cell infiltration into the tumor microenvironment. Cancer Res 72:876–886PubMedCrossRef
82.
go back to reference Zollo M, Di Dato V, Spano D et al (2012) Targeting monocyte chemotactic protein-1 synthesis with bindarit induces tumor regression in prostate and breast cancer animal models. Clin Exp Metastasis 29:585–601PubMedCrossRef Zollo M, Di Dato V, Spano D et al (2012) Targeting monocyte chemotactic protein-1 synthesis with bindarit induces tumor regression in prostate and breast cancer animal models. Clin Exp Metastasis 29:585–601PubMedCrossRef
83.
go back to reference Obermajer N, Muthuswamy R, Odunsi K et al (2011) PGE(2)-induced CXCL12 production and CXCR4 expression controls the accumulation of human MDSCs in ovarian cancer environment. Cancer Res 71:7463–7470PubMedCrossRef Obermajer N, Muthuswamy R, Odunsi K et al (2011) PGE(2)-induced CXCL12 production and CXCR4 expression controls the accumulation of human MDSCs in ovarian cancer environment. Cancer Res 71:7463–7470PubMedCrossRef
84.
85.
go back to reference 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 87:713–725PubMedCrossRef 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 87:713–725PubMedCrossRef
86.
go back to reference Ichikawa M, Williams R, Wang L et al (2011) S100A8/A9 activate key genes and pathways in colon tumor progression. Mol Cancer Res 9:133–148PubMedCrossRef Ichikawa M, Williams R, Wang L et al (2011) S100A8/A9 activate key genes and pathways in colon tumor progression. Mol Cancer Res 9:133–148PubMedCrossRef
87.
go back to reference Sawanobori Y, Ueha S, Kurachi M et al (2008) Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice. Blood 111:5457–5466PubMedCrossRef Sawanobori Y, Ueha S, Kurachi M et al (2008) Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice. Blood 111:5457–5466PubMedCrossRef
88.
go back to reference Kato M, Takahashi M, Akhand AA et al (1998) Transgenic mouse model for skin malignant melanoma. Oncogene 17:1885–1888PubMedCrossRef Kato M, Takahashi M, Akhand AA et al (1998) Transgenic mouse model for skin malignant melanoma. Oncogene 17:1885–1888PubMedCrossRef
89.
go back to reference Lengagne R, Le Gal FA, Garcette M et al (2004) Spontaneous vitiligo in an animal model for human melanoma: role of tumor-specific CD8+ T cells. Cancer Res 15:1496–1501CrossRef Lengagne R, Le Gal FA, Garcette M et al (2004) Spontaneous vitiligo in an animal model for human melanoma: role of tumor-specific CD8+ T cells. Cancer Res 15:1496–1501CrossRef
90.
go back to reference Umansky V, Abschuetz O, Osen W et al (2008) Melanoma-specific memory T cells are functionally active in Ret transgenic mice without macroscopic tumors. Cancer Res 68:9451–9458PubMedCrossRef Umansky V, Abschuetz O, Osen W et al (2008) Melanoma-specific memory T cells are functionally active in Ret transgenic mice without macroscopic tumors. Cancer Res 68:9451–9458PubMedCrossRef
91.
go back to reference Zhao F, Falk C, Osen W et al (2009) Activation of p38 mitogen-activated protein kinase drives dendritic cells to become tolerogenic in ret transgenic mice spontaneously developing melanoma. Clin Cancer Res 15:4382–4390PubMedCrossRef Zhao F, Falk C, Osen W et al (2009) Activation of p38 mitogen-activated protein kinase drives dendritic cells to become tolerogenic in ret transgenic mice spontaneously developing melanoma. Clin Cancer Res 15:4382–4390PubMedCrossRef
92.
go back to reference Whiteside TL (2004) Down-regulation of zeta-chain expression in T cells: a biomarker of prognosis in cancer? Cancer Immunol Immunother 53:865–878PubMed Whiteside TL (2004) Down-regulation of zeta-chain expression in T cells: a biomarker of prognosis in cancer? Cancer Immunol Immunother 53:865–878PubMed
93.
go back to reference Boniface JD, Poschke I, Mao Y et al (2011) Tumor-dependent down-regulation of the ζ-chain in T-cells is detectable in early breast cancer and correlates with immune cell function. Int J Cancer 131:129–139PubMedCrossRef Boniface JD, Poschke I, Mao Y et al (2011) Tumor-dependent down-regulation of the ζ-chain in T-cells is detectable in early breast cancer and correlates with immune cell function. Int J Cancer 131:129–139PubMedCrossRef
94.
go back to reference Baniyash M (2004) TCR zeta-chain downregulation: curtailing an excessive inflammatory immune response. Nat Rev Immunol 4:675–687PubMedCrossRef Baniyash M (2004) TCR zeta-chain downregulation: curtailing an excessive inflammatory immune response. Nat Rev Immunol 4:675–687PubMedCrossRef
95.
go back to reference Qu P, Du H, Li Y et al (2009) Myeloid-specific expression of Api6/AIM/Sp alpha induces systemic inflammation and adenocarcinoma in the lung. J Immunol 182:1648–1659PubMed Qu P, Du H, Li Y et al (2009) Myeloid-specific expression of Api6/AIM/Sp alpha induces systemic inflammation and adenocarcinoma in the lung. J Immunol 182:1648–1659PubMed
96.
go back to reference 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 37:423–430PubMedCrossRef 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 37:423–430PubMedCrossRef
97.
go back to reference Sinha P, Okoro C, Foell D et al (2008) Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells. J Immunol 181:4666–4675PubMed Sinha P, Okoro C, Foell D et al (2008) Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells. J Immunol 181:4666–4675PubMed
98.
go back to reference Kao J, Ko EC, Eisenstein S et al (2011) Targeting immune suppressing myeloid-derived suppressor cells in oncology. Crit Rev Oncol Hematol 77:12–19PubMedCrossRef Kao J, Ko EC, Eisenstein S et al (2011) Targeting immune suppressing myeloid-derived suppressor cells in oncology. Crit Rev Oncol Hematol 77:12–19PubMedCrossRef
99.
go back to reference Ozao-Choy J, Ma G, Kao J et al (2009) The novel role of tyrosine kinase inhibitor in the reversal of immune suppression and modulation of tumor microenvironment for immune-based cancer therapies. Cancer Res 69:2514–2522PubMedCrossRef Ozao-Choy J, Ma G, Kao J et al (2009) The novel role of tyrosine kinase inhibitor in the reversal of immune suppression and modulation of tumor microenvironment for immune-based cancer therapies. Cancer Res 69:2514–2522PubMedCrossRef
100.
go back to reference 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 70:3526–3536PubMedCrossRef 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 70:3526–3536PubMedCrossRef
101.
go back to reference Ko JS, Zea AH, Rini BI et al (2009) Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res 15:2148–2157PubMedCrossRef Ko JS, Zea AH, Rini BI et al (2009) Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res 15:2148–2157PubMedCrossRef
102.
go back to reference Mirza N, Fishman M, Fricke I et al (2006) All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients. Cancer Res 66:9299–9307PubMedCrossRef Mirza N, Fishman M, Fricke I et al (2006) All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients. Cancer Res 66:9299–9307PubMedCrossRef
103.
go back to reference Michels T, Shurin GV, Naiditch H et al (2012) Paclitaxel promotes differentiation of myeloid-derived suppressor cells into dendritic cells in vitro in a TLR4-independent manner. J Immunotoxicol 9:292–300PubMedCrossRef Michels T, Shurin GV, Naiditch H et al (2012) Paclitaxel promotes differentiation of myeloid-derived suppressor cells into dendritic cells in vitro in a TLR4-independent manner. J Immunotoxicol 9:292–300PubMedCrossRef
104.
go back to reference Friedman A (2007) Transcriptional control of granulocyte and monocyte development. Oncogene 26:6816–6828PubMedCrossRef Friedman A (2007) Transcriptional control of granulocyte and monocyte development. Oncogene 26:6816–6828PubMedCrossRef
105.
go back to reference Song X, Ye D, Liu B et al (2009) Combination of all-trans retinoic acid and a human papillomavirus therapeutic vaccine suppresses the number and function of immature myeloid cells and enhances antitumor immunity. Cancer Sci 100:334–340PubMedCrossRef Song X, Ye D, Liu B et al (2009) Combination of all-trans retinoic acid and a human papillomavirus therapeutic vaccine suppresses the number and function of immature myeloid cells and enhances antitumor immunity. Cancer Sci 100:334–340PubMedCrossRef
106.
go back to reference Shurin MR, Naiditch H, Gutkin DW et al (2012) ChemoImmunoModulation: immune regulation by the antineoplastic chemotherapeutic agents. Curr Med Chem 19:1792–1803PubMedCrossRef Shurin MR, Naiditch H, Gutkin DW et al (2012) ChemoImmunoModulation: immune regulation by the antineoplastic chemotherapeutic agents. Curr Med Chem 19:1792–1803PubMedCrossRef
107.
go back to reference Sevko A, Kremer V, Falk C et al (2012) Application of paclitaxel in low non-cytotoxic doses supports vaccination with melanoma antigens in normal mice. J Immunotoxicol 9:275–281PubMedCrossRef Sevko A, Kremer V, Falk C et al (2012) Application of paclitaxel in low non-cytotoxic doses supports vaccination with melanoma antigens in normal mice. J Immunotoxicol 9:275–281PubMedCrossRef
108.
go back to reference Suzuki E, Kapoor V, Jassar AS et al (2005) Gemcitabine selectively eliminates splenic Gr-1+/CD11b + myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res 11:6713–6721PubMedCrossRef Suzuki E, Kapoor V, Jassar AS et al (2005) Gemcitabine selectively eliminates splenic Gr-1+/CD11b + myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res 11:6713–6721PubMedCrossRef
109.
go back to reference Vincent J, Mignot G, Chalmin F et al (2010) 5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity. Cancer Res 70:3052–3061PubMedCrossRef Vincent J, Mignot G, Chalmin F et al (2010) 5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity. Cancer Res 70:3052–3061PubMedCrossRef
110.
go back to reference Boelte KC, Gordy LE, Joyce S et al (2011) Rgs2 mediates pro-angiogenic function of myeloid derived suppressor cells in the tumor microenvironment via upregulation of MCP-1. PLoS One 6:e18534PubMedCrossRef Boelte KC, Gordy LE, Joyce S et al (2011) Rgs2 mediates pro-angiogenic function of myeloid derived suppressor cells in the tumor microenvironment via upregulation of MCP-1. PLoS One 6:e18534PubMedCrossRef
111.
go back to reference Ghofrani HA, Osterloh IH, Grimminger F (2006) Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond. Nat Rev Drug Discov 5:689–702PubMedCrossRef Ghofrani HA, Osterloh IH, Grimminger F (2006) Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond. Nat Rev Drug Discov 5:689–702PubMedCrossRef
112.
go back to reference Capuano G, Rigamonti N, Grioni M, Freschi M, Bellone M (2009) Modulators of arginine metabolism support cancer immunosurveillance. BMC Immunol 10:1PubMedCrossRef Capuano G, Rigamonti N, Grioni M, Freschi M, Bellone M (2009) Modulators of arginine metabolism support cancer immunosurveillance. BMC Immunol 10:1PubMedCrossRef
113.
go back to reference Serafini P, Meckel K, Kelso M et al (2006) Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J Exp Med 203:2691–2702PubMedCrossRef Serafini P, Meckel K, Kelso M et al (2006) Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J Exp Med 203:2691–2702PubMedCrossRef
114.
go back to reference Ugel S, Delpozzo F, Desantis G et al (2009) Therapeutic targeting of myeloid-derived suppressor cells. Curr Opin Pharmacol 9:470–481PubMedCrossRef Ugel S, Delpozzo F, Desantis G et al (2009) Therapeutic targeting of myeloid-derived suppressor cells. Curr Opin Pharmacol 9:470–481PubMedCrossRef
115.
go back to reference De Santo C, Serafini P, Marigo I et al (2005) Nitroaspirin corrects immune dysfunction in tumor-bearing hosts and promotes tumor eradication by cancer vaccination. Proc Natl Acad Sci U S A 102:4185–4190PubMedCrossRef De Santo C, Serafini P, Marigo I et al (2005) Nitroaspirin corrects immune dysfunction in tumor-bearing hosts and promotes tumor eradication by cancer vaccination. Proc Natl Acad Sci U S A 102:4185–4190PubMedCrossRef
116.
go back to reference Jayaraman P, Parikh F, Lopez-Rivera E et al (2012) Tumor-expressed inducible nitric oxide synthase controls induction of functional myeloid-derived suppressor cells through modulation of vascular endothelial growth factor release. J Immunol 188:5365–5376PubMedCrossRef Jayaraman P, Parikh F, Lopez-Rivera E et al (2012) Tumor-expressed inducible nitric oxide synthase controls induction of functional myeloid-derived suppressor cells through modulation of vascular endothelial growth factor release. J Immunol 188:5365–5376PubMedCrossRef
117.
go back to reference Veltman JD, Lambers ME, van Nimwegen M et al (2010) COX-2 inhibition improves immunotherapy and is associated with decreased numbers of myeloid-derived suppressor cells in mesothelioma. Celecoxib influences MDSC function. BMC Cancer 10:464PubMedCrossRef Veltman JD, Lambers ME, van Nimwegen M et al (2010) COX-2 inhibition improves immunotherapy and is associated with decreased numbers of myeloid-derived suppressor cells in mesothelioma. Celecoxib influences MDSC function. BMC Cancer 10:464PubMedCrossRef
118.
go back to reference Fujita M, Kohanbash G, Fellows-Mayle W et al (2011) COX-2 blockade suppresses gliomagenesis by inhibiting myeloid-derived suppressor cells. Cancer Res 71:2664–2674PubMedCrossRef Fujita M, Kohanbash G, Fellows-Mayle W et al (2011) COX-2 blockade suppresses gliomagenesis by inhibiting myeloid-derived suppressor cells. Cancer Res 71:2664–2674PubMedCrossRef
119.
go back to reference Ochoa AC, Zea A, Hernandez C (2007) Arginase, prostaglandins, and myeloid-derived suppressor cells in renal cell carcinoma. Clin Cancer Res 13:721s–726sPubMedCrossRef Ochoa AC, Zea A, Hernandez C (2007) Arginase, prostaglandins, and myeloid-derived suppressor cells in renal cell carcinoma. Clin Cancer Res 13:721s–726sPubMedCrossRef
Metadata
Title
Tumor Microenvironment and Myeloid-Derived Suppressor Cells
Authors
Viktor Umansky
Alexandra Sevko
Publication date
01-08-2013
Publisher
Springer Netherlands
Published in
Cancer Microenvironment / Issue 2/2013
Print ISSN: 1875-2292
Electronic ISSN: 1875-2284
DOI
https://doi.org/10.1007/s12307-012-0126-7

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