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Derangement of immune responses by myeloid suppressor cells

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Abstract

In tumor-bearing mice and cancer patients, tumor progression is often associated with altered hematopoiesis leading to the accumulation of myeloid cells. Extensive studies in preclinical models indicate that these cells share the CD11b and the Gr-1 markers, possess a mixed mature-immature myeloid phenotype, and are responsible for the induction of T-cell dysfunctions, both tumor-specific and nonspecific. Moreover, CD11b+Gr-1+ myeloid cells are described under different unrelated situations associated with temporary impairment of the T-lymphocyte reactivity. This review examines recent findings on the nature, properties, and mechanisms of action of these myeloid suppressor cells (MSCs).

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References

  1. Ahlers JD, Belyakov IM, Terabe M, Koka R, Donaldson DD, Thomas EK, Berzofsky JA (2002) A push-pull approach to maximize vaccine efficacy: abrogating suppression with an IL-13 inhibitor while augmenting help with granulocyte/macrophage colony-stimulating factor and CD40L. Proc Natl Acad Sci U S A 99:13020

    CAS  PubMed  Google Scholar 

  2. al Ramadi BK, Greene JM, Meissler JJ Jr, Eisenstein TK (1992) Immunosuppression induced by attenuated Salmonella: effect of LPS responsiveness on development of suppression. Microb Pathog 12:267

    PubMed  Google Scholar 

  3. Albina JE, Abate JA, Mastrofrancesco B (1993) Role of ornithine as a proline precursor in healing wounds. J Surg Res 55:97

    CAS  PubMed  Google Scholar 

  4. Almand B, Resser JR, Lindman B, Nadaf S, Clark JI, Kwon ED, Carbone DP, Gabrilovich DI (2000) Clinical significance of defective dendritic cell differentiation in cancer. Clin Cancer Res 6:1755

    CAS  PubMed  Google Scholar 

  5. Almand B, Clark JI, Nikitina E, van Beynen J, English NR, Knight SC, Carbone DP, Gabrilovich DI (2001) Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol 166:678

    CAS  PubMed  Google Scholar 

  6. Angulo I, de las Heras FG, Garcia-Bustos JF, Gargallo D, Munoz-Fernandez MA, Fresno M (2000) Nitric oxide-producing CD11b(+)Ly-6G(Gr-1)(+)CD31(ER-MP12)(+) cells in the spleen of cyclophosphamide-treated mice: implications for T-cell responses in immunosuppressed mice. Blood 95:212

    CAS  PubMed  Google Scholar 

  7. Angulo I, Rullas J, Campillo JA, Obregon E, Heath A, Howard M, Munoz-Fernandez MA, Subiza JL (2000) Early myeloid cells are high producers of nitric oxide upon CD40 plus IFN-gamma stimulation through a mechanism dependent on endogenous TNF-alpha and IL-1alpha. Eur J Immunol 30:1263

    CAS  PubMed  Google Scholar 

  8. Anichini A, Molla A, Mortarini R, Tragni G, Bersani I, Di Nicola M, Gianni AM, Pilotti S, Dunbar R, Cerundolo V, Parmiani G (1999) An expanded peripheral T cell population to a cytotoxic T lymphocyte (CTL)-defined, melanocyte-specific antigen in metastatic melanoma patients impacts on generation of peptide-specific CTLs but does not overcome tumor escape from immune surveillance in metastatic lesions. J Exp Med 190:651

    CAS  PubMed  Google Scholar 

  9. Apolloni E, Bronte V, Mazzoni A, Serafini P, Cabrelle A, Segal DM, Young HA, Zanovello P (2000) Immortalized myeloid suppressor cells trigger apoptosis in antigen-activated T lymphocytes. J Immunol 165:6723

    CAS  PubMed  Google Scholar 

  10. Asselin-Paturel C, Boonstra A, Dalod M, Durand I, Yessaad N, Dezutter-Dambuyant C, Vicari A, O’Garra A, Biron C, Briere F, Trinchieri G (2001) Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology. Nat Immunol 2:1144

    Article  CAS  PubMed  Google Scholar 

  11. Berzofsky JA, Ahlers JD, Belyakov IM (2001) Strategies for designing and optimizing new generation vaccines. Nat Rev Immunol 1:209

    CAS  PubMed  Google Scholar 

  12. Billiau AD, Fevery S, Rutgeerts O, Landuyt W, Waer M (2003) Transient expansion of Mac1+ Ly6-G+ Ly6-C+ early myeloid cells with suppressor activity in spleens of murine radiation marrow chimeras: possible implications for the graft-versus-host and graft-versus-leukemia reactivity of donor lymphocyte infusions. Blood 3:3

    Google Scholar 

  13. Bobe P, Benihoud K, Grandjon D, Opolon P, Pritchard LL, Huchet R (1999) Nitric oxide mediation of active immunosuppression associated with graft-versus-host reaction. Blood 94:1028

    CAS  PubMed  Google Scholar 

  14. Brito C, Naviliat M, Tiscornia AC, Vuillier F, Gualco G, Dighiero G, Radi R, Cayota AM (1999) Peroxynitrite inhibits T lymphocyte activation and proliferation by promoting impairment of tyrosine phosphorylation and peroxynitrite-driven apoptotic death. J Immunol 162:3356

    CAS  PubMed  Google Scholar 

  15. Bronte V, Wang M, Overwijk WW, Surman DR, Pericle F, Rosenberg SA, Restifo NP (1998) Apoptotic death of CD8+ T lymphocytes after immunization: induction of a suppressive population of Mac-1+/Gr-1+ cells. J Immunol 161:5313

    CAS  PubMed  Google Scholar 

  16. Bronte V, Chappel DB, Apolloni E, Cabrelle A, Wang M, Hwu P, Restifo NP (1999) Unopposed production of granulocyte-macrophage colony-stimulating factor by tumors inhibits CD8+ T cell responses by dysregulating antigen-presenting cell maturation. J Immunol 162:5728

    CAS  PubMed  Google Scholar 

  17. Bronte V, Apolloni E, Cabrelle A, Ronca R, Serafini A, Zamboni P, Restifo NP, Zanovello P (2000) Identification of a CD11b+/Gr-1+/CD31+ myeloid progenitor capable of activating or suppressing CD8+ T cells. Blood 96:3838

    CAS  PubMed  Google Scholar 

  18. Bronte V, Serafini P, Apolloni E, Zanovello P (2001) Tumor-induced immune dysfunctions caused by myeloid suppressor cells. J Immunother 24:431

    Article  CAS  PubMed  Google Scholar 

  19. Bronte V, Serafini P, De Santo C, Marigo I, Tosello V, Mazzoni A, Segal DM, Staib C, Lowel M, Sutter G, Colombo MP, Zanovello P (2003) IL-4-induced arginase 1 suppresses alloreactive T cells in tumor- bearing mice. J Immunol 170:270

    CAS  PubMed  Google Scholar 

  20. Bronte V, Serafini P, Mazzoni A, Segal DM, Zanovello P (2003) L-arginine metabolism in myeloid cells controls T-lymphocyte functions. Trends Immunol 24:301

    Article  Google Scholar 

  21. Cauley LS, Miller EE, Yen M, Swain SL (2000) Superantigen-induced CD4 T cell tolerance mediated by myeloid cells and IFN-gamma. J Immunol 165:6056

    CAS  PubMed  Google Scholar 

  22. Chang CI, Liao JC, Kuo L (2001) Macrophage arginase promotes tumor cell growth and suppresses nitric oxide-mediated tumor cytotoxicity. Cancer Res 61:1100

    CAS  PubMed  Google Scholar 

  23. Colleluori DM, Ash DE (2001) Classical and slow-binding inhibitors of human type II arginase. Biochemistry 40:9356

    CAS  PubMed  Google Scholar 

  24. de Jonge WJ, Kwikkers KL, te Velde AA, van Deventer SJ, Nolte MA, Mebius RE, Ruijter JM, Lamers MC, Lamers WH (2002) Arginine deficiency affects early B cell maturation and lymphoid organ development in transgenic mice. J Clin Invest 110:1539

    PubMed  Google Scholar 

  25. Fleming TJ, Fleming ML, T. R. Malek TR (1993) Selective expression of Ly-6G on myeloid lineage cells in mouse bone marrow. RB6-8C5 mAb to granulocyte-differentiation antigen (Gr-1) detects members of the Ly-6 family. J Immunol 151:2399

    CAS  PubMed  Google Scholar 

  26. Gabrilovich DI, Velders MP, Sotomayor EM, Kast WM. (2001) Mechanism of immune dysfunction in cancer mediated by immature gr-1(+) myeloid cells. J Immunol 166:5398

    CAS  PubMed  Google Scholar 

  27. Garrity T, Pandit R, Wright MA, Benefield J, Keni S, Young MR (1997) Increased presence of CD34+ cells in the peripheral blood of head and neck cancer patients and their differentiation into dendritic cells. Int J Cancer 73:663

    CAS  PubMed  Google Scholar 

  28. Geldhof AB, Van Ginderachter JA, Liu Y, Noel W, Raes G, De Baetselier P (2002) Antagonistic effect of NK cells on alternatively activated monocytes: a contribution of NK cells to CTL generation. Blood 100:4049

    CAS  PubMed  Google Scholar 

  29. Goni O, Alcaide P, Fresno M (2002) Immunosuppression during acute Trypanosoma cruzi infection: involvement of Ly6G (Gr1(+))CD11b(+ )immature myeloid suppressor cells. Int Immunol 14:1125

    CAS  PubMed  Google Scholar 

  30. Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3:23

    CAS  PubMed  Google Scholar 

  31. Gu L, Tseng S, Horner RM, Tam C, Loda M, Rollins BJ (2000) Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1. Nature 404:407

    CAS  PubMed  Google Scholar 

  32. Horiguchi S, Petersson M, Nakazawa T, Kanda M, Zea AH, Ochoa AC, Kiessling R (1999) Primary chemically induced tumors induce profound immunosuppression concomitant with apoptosis and alterations in signal transduction in T cells and NK cells. Cancer Res 59:2950

    CAS  PubMed  Google Scholar 

  33. Jaffe ML, Arai H, Nabel GJ (1996) Mechanisms of tumor-induced immunosuppression: evidence for contact-dependent T cell suppression by monocytes. Mol Med 2:692

    CAS  PubMed  Google Scholar 

  34. Kiessling R, Wasserman K, Horiguchi S, Kono K, Sjoberg J, Pisa P, Petersson M (1999) Tumor-induced immune dysfunction. Cancer Immunol Immunother 48:353

    Article  CAS  PubMed  Google Scholar 

  35. Kobayashi M, Kobayashi H, Pollard RB, Suzuki F(1998) A pathogenic role of Th2 cells and their cytokine products on the pulmonary metastasis of murine B16 melanoma. J Immunol 160:5869

    CAS  PubMed  Google Scholar 

  36. Koblish HK, Hunter CA, Wysocka M, Trinchieri G, Lee WM (1998) Immune suppression by recombinant interleukin (rIL)-12 involves interferon gamma induction of nitric oxide synthase 2 (iNOS) activity: inhibitors of NO generation reveal the extent of rIL-12 vaccine adjuvant effect. J Exp Med 188:1603

    Article  CAS  PubMed  Google Scholar 

  37. Kono K, Salazar-Onfray F, Petersson M, Hansson J, Masucci G, Wasserman K, Nakazawa T, Anderson P, Kiessling R (1996) Hydrogen peroxide secreted by tumor-derived macrophages down-modulates signal-transducing zeta molecules and inhibits tumor-specific T cell- and natural killer cell-mediated cytotoxicity. Eur J Immunol 26:1308

    CAS  PubMed  Google Scholar 

  38. Korsgren M, Persson CG, Sundler F, Bjerke T, Hansson T, Chambers BJ, Hong S, Van Kaer L, Ljunggren HG, Korsgren O (1999) Natural killer cells determine development of allergen-induced eosinophilic airway inflammation in mice. J Exp Med 189:553

    CAS  PubMed  Google Scholar 

  39. Kos FJ (1998) Regulation of adaptive immunity by natural killer cells. Immunol Res 17:303

    CAS  PubMed  Google Scholar 

  40. Kusmartsev S, Gabrilovich DI (2002) Immature myeloid cells and cancer-associated immune suppression. Cancer Immunol Immunother 51:293

    CAS  PubMed  Google Scholar 

  41. Kusmartsev SA, Li Y, Chen SH (2000) Gr-1+ myeloid cells derived from tumor-bearing mice inhibit primary T cell activation induced through CD3/CD28 costimulation. J Immunol 165:779

    CAS  PubMed  Google Scholar 

  42. Lagasse E, Weissman IL (1996) Flow cytometric identification of murine neutrophils and monocytes. J Immunol Methods 197:139

    CAS  PubMed  Google Scholar 

  43. Lee KH, Wang E, Nielsen MB, Wunderlich J, Migueles S, Connors M, Steinberg SM, Rosenberg SA, Marincola FM (1999) Increased vaccine-specific T cell frequency after peptide-based vaccination correlates with increased susceptibility to in vitro stimulation but does not lead to tumor regression. J Immunol 163:6292

    CAS  PubMed  Google Scholar 

  44. Leenen PJ, de Bruijn MF, Voerman JS, Campbell PA, van Ewijk W (1994) Markers of mouse macrophage development detected by monoclonal antibodies. J Immunol Methods 174:5

    CAS  PubMed  Google Scholar 

  45. Leite-de-Moraes MC, Lisbonne M, Arnould A, Machavoine F, Herbelin A, Dy M, Schneider E (2002) Ligand-activated natural killer T lymphocytes promptly produce IL-3 and GM-CSF in vivo: relevance to peripheral myeloid recruitment. Eur J Immunol 32:1897

    CAS  PubMed  Google Scholar 

  46. Liu Y, Van Ginderachter JA, Brys L, De Baetselier P, Raes G, Geldhof AB (2003) Nitric oxide-independent CTL suppression during tumor progression: association with arginase-producing (M2) myeloid cells. J Immunol 170:5064

    CAS  PubMed  Google Scholar 

  47. Maier T, Holda JH, Claman HN (1989) Natural suppressor cells. Prog Clin Biol Res 288:235

    CAS  PubMed  Google Scholar 

  48. Mantovani A, Sozzani S, Locati M, Allavena P, Sica A (2002) Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23:549

    CAS  PubMed  Google Scholar 

  49. Marshall MA, Jankovic D, Maher VE, Sher A, Berzofsky JA (2001) Mice infected with Schistosoma mansoni develop a novel non-T-lymphocyte suppressor population which inhibits virus-specific CTL induction via a soluble factor. Microbes Infect 3:1051

    CAS  PubMed  Google Scholar 

  50. Mazzoni A, Bronte V, Visintin A, Spitzer JH, Apolloni E, Serafini P, Zanovello P, Segal DM (2002) Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism. J Immunol 168:689

    CAS  PubMed  Google Scholar 

  51. McKnight AJ, Gordon S (1998) Membrane molecules as differentiation antigens of murine macrophages. Adv Immunol 68:271

    CAS  PubMed  Google Scholar 

  52. Melani C, Chiodoni C, Forni G, Colombo MP (2003) Myeloid cell expansion elicited by the progression of spontaneous mammary carcinomas in c-erbB-2 transgenic BALB/c mice suppresses immune reactivity. Blood 15:15

    Google Scholar 

  53. Mellstedt H, Fagerberg J, Frodin JE, Henriksson L, Hjelm-Skoog AL, Liljefors M, Ragnhammar P, Shetye J, Osterborg A (1999) Augmentation of the immune response with granulocyte-macrophage colony-stimulating factor and other hematopoietic growth factors. Curr Opin Hematol 6:169

    CAS  PubMed  Google Scholar 

  54. Mencacci A, Montagnoli C, Bacci A, Cenci E, Pitzurra L, Spreca A, Kopf M, Sharpe AH, Romani L (2002) CD80+Gr-1+ myeloid cells inhibit development of antifungal Th1 immunity in mice with candidiasis. J Immunol 169:3180

    CAS  PubMed  Google Scholar 

  55. Mills CD, Shearer J, Evans R, Caldwell MD (1992) Macrophage arginine metabolism and the inhibition or stimulation of cancer. J Immunol 149:2709

    CAS  PubMed  Google Scholar 

  56. Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AM (2000) M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol 164:6166

    CAS  PubMed  Google Scholar 

  57. Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, Burg G, Schadendorf D (1998) Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med 4:328

    CAS  PubMed  Google Scholar 

  58. Nielsen MB, Marincola FM (2000) Melanoma vaccines: the paradox of T cell activation without clinical response. Cancer Chemother Pharmacol 46:S62

    CAS  PubMed  Google Scholar 

  59. Ochoa JB, Strange J, Kearney P, Gellin G, Endean E, Fitzpatrick E (2001) Effects of L-arginine on the proliferation of T lymphocyte subpopulations. JPEN J Parenter Enteral Nutr 25:23

    CAS  PubMed  Google Scholar 

  60. O’Keeffe M, Hochrein H, Vremec D, Caminschi I, Miller JL, Anders EM, Wu L, Lahoud MH, Henri S, Scott B, Hertzog P, Tatarczuch L, Shortman K (2002) Mouse plasmacytoid cells: long-lived cells, heterogeneous in surface phenotype and function, that differentiate into CD8(+) dendritic cells only after microbial stimulus. J Exp Med 196:1307

    Article  CAS  PubMed  Google Scholar 

  61. Pak AS, Wright MA, Matthews JP, Collins SL, Petruzzelli GJ, Young MRI (1995) Mechanisms of immune suppression in patients with head and neck cancer: presence of CD34(+) cells which suppress immune functions within cancers that secrete granulocyte-macrophage colony-stimulating factor. Clin Cancer Res 1:95

    CAS  PubMed  Google Scholar 

  62. Pelaez B, Campillo JA, Lopez-Asenjo JA, Subiza JL (2001) Cyclophosphamide induces the development of early myeloid cells suppressing tumor cell growth by a nitric oxide-dependent mechanism. J Immunol 166:6608

    CAS  PubMed  Google Scholar 

  63. Pericle F, Kirken RA, Bronte V, Sconocchia G, DaSilva L, Segal DM (1997) Immunocompromised tumor-bearing mice show a selective loss of STAT5a/b expression in T and B lymphocytes. J Immunol 159:2580

    CAS  PubMed  Google Scholar 

  64. Prins HA, Houdijk AP, Nijveldt RJ, Teerlink T, Huygens P, Thijs LG, van Leeuwen PA (2001) Arginase release from red blood cells: possible link in transfusion induced immune suppression? Shock 16:113

    CAS  PubMed  Google Scholar 

  65. Prins RM, Scott GP, Merchant RE, Graf MR (2002) Irradiated tumor cell vaccine for treatment of an established glioma. II. Expansion of myeloid suppressor cells that promote tumor progression. Cancer Immunol Immunother 51:190

    PubMed  Google Scholar 

  66. Radoja S, Rao TD, Hillman D, Frey AB (2000) Mice bearing late-stage tumors have normal functional systemic T cell responses in vitro and in vivo. J Immunol 164:2619

    CAS  PubMed  Google Scholar 

  67. Rodriguez PC, Zea AH, Culotta KS, Zabaleta J, Ochoa JB, Ochoa AC (2002) Regulation of T cell receptor CD3zeta chain expression by L-arginine. J Biol Chem 277:21123

    CAS  PubMed  Google Scholar 

  68. Saio M, Radoja S, Marino M, Frey AB (2001) Tumor-infiltrating macrophages induce apoptosis in activated CD8(+) T cells by a mechanism requiring cell contact and mediated by both the cell-associated form of TNF and nitric oxide. J Immunol 167:5583

    CAS  PubMed  Google Scholar 

  69. Salvadori S, Martinelli G, Zier K (2000) Resection of solid tumors reverses T cell defects and restores protective immunity. J Immunol 164:2214

    CAS  PubMed  Google Scholar 

  70. Seo N, Hayakawa S, Takigawa M, Tokura Y (2001) Interleukin-10 expressed at early tumour sites induces subsequent generation of CD4(+) T-regulatory cells and systemic collapse of antitumour immunity. Immunology 103:449

    CAS  PubMed  Google Scholar 

  71. Seung LP, Rowley DA, Dubey P, Schreiber H (1995) Synergy between T-cell immunity and inhibition of paracrine stimulation causes tumor rejection. Proc Natl Acad Sci U S A 92:6254

    CAS  PubMed  Google Scholar 

  72. Smyth MJ, Godfrey DI (2000) NKT cells and tumor immunity--a double-edged sword. Nat Immunol 1:459

    CAS  PubMed  Google Scholar 

  73. Strober S (1984) Natural suppressor (NS) cells, neonatal tolerance, and total lymphoid irradiation: exploring obscure relationships. Annu Rev Immunol 2:219

    CAS  PubMed  Google Scholar 

  74. Subiza JL, Vinuela JE, Rodriguez R, Gil J, Figueredo MA, De La Concha EG (1989) Development of splenic natural suppressor (NS) cells in Ehrlich tumor-bearing mice. Int J Cancer 44:307

    CAS  PubMed  Google Scholar 

  75. Suh H, Wadhwa NK, Peresleni T, McNurlan M, Garlick P, Goligorsky MS (1997) Decreased L-arginine during peritonitis in ESRD patients on peritoneal dialysis. Adv Perit Dial 13:205

    CAS  PubMed  Google Scholar 

  76. Tatsumi T, Kierstead LS, Ranieri E, Gesualdo L, Schena FP, Finke JH, Bukowski RM, Mueller-Berghaus J, Kirkwood JM, Kwok WW, Storkus WJ (2002) Disease-associated bias in T helper type 1 (Th1)/Th2 CD4(+) T cell responses against MAGE-6 in HLA-DRB10401(+) patients with renal cell carcinoma or melanoma. J Exp Med 196:619

    CAS  PubMed  Google Scholar 

  77. Terabe M, Matsui S, Noben-Trauth N, Chen H, Watson C, Donaldson DD, Carbone DP, Paul WE, Berzofsky JA (2000) NKT cell-mediated repression of tumor immunosurveillance by IL-13 and the IL-4R-STAT6 pathway. Nat Immunol 1:515

    CAS  PubMed  Google Scholar 

  78. Terrazas LI, Walsh KL, Piskorska D, McGuire E, Harn DA Jr (2001) The schistosome oligosaccharide lacto-N-neotetraose expands Gr1(+) cells that secrete anti-inflammatory cytokines and inhibit proliferation of naive CD4(+) cells: a potential mechanism for immune polarization in helminth infections. J Immunol 167:5294

    CAS  PubMed  Google Scholar 

  79. Toi M, Taniguchi T, Yamamoto Y, Kurisaki T, Suzuki H, Tominaga T (1996) Clinical significance of the determination of angiogenic factors. Eur J Cancer 32A:2513

    CAS  PubMed  Google Scholar 

  80. Vallance P, Leiper J (2002) Blocking NO synthesis: how, where and why? Nat Rev Drug Discov 1:939

    CAS  PubMed  Google Scholar 

  81. Warren TL, Weiner GJ (2000) Uses of granulocyte-macrophage colony-stimulating factor in vaccine development. Curr Opin Hematol 7:168

    Google Scholar 

  82. Wright MA, Wiers K, Vellody K, Djordjevic D, Young MR (1998) Stimulation of immune suppressive CD34+ cells from normal bone marrow by Lewis lung carcinoma tumors. Cancer Immunol Immunother 46:253

    CAS  PubMed  Google Scholar 

  83. Wu G, Morris SM Jr (1998) Arginine metabolism: nitric oxide and beyond. Biochem J 336:1

    CAS  PubMed  Google Scholar 

  84. Young MR, Ihm J, Lozano Y, Wright MA, Prechel MM (1995) Treating tumor-bearing mice with vitamin D3 diminishes tumor- induced myelopoiesis and associated immunosuppression, and reduces tumor metastasis and recurrence. Cancer Immunol Immunother 41:37

    CAS  PubMed  Google Scholar 

  85. Young MR, Lozano Y, Ihm J, Wright MA, Prechel MM (1996) Vitamin D3 treatment of tumor bearers can stimulate immune competence and reduce tumor growth when treatment coincides with a heightened presence of natural suppressor cells. Cancer Lett 104:153

    CAS  PubMed  Google Scholar 

  86. Young MR, Wright MA, Matthews JP, Malik I, Prechel M (1996) Suppression of T cell proliferation by tumor-induced granulocyte-macrophage progenitor cells producing transforming growth factor-beta and nitric oxide. J Immunol 156:1916

    CAS  PubMed  Google Scholar 

  87. Young MR, Wright MA, Lozano Y, Prechel MM, Benefield J, Leonetti JP, Collins SL, Petruzzelli GJ (1997) Increased recurrence and metastasis in patients whose primary head and neck squamous cell carcinomas secreted granulocyte-macrophage colony-stimulating factor and contained CD34+ natural suppressor cells. Int J Cancer 74:69

    CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank Kimberly Noonan for her critical reading of the manuscript.

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Authors and Affiliations

  1. Department of Oncology and Surgical Sciences, Oncology Section, Azienda Ospedaliera, Via Gattamelata 64, 35128, Padova, Italy

    Paolo Serafini, Carmela De Santo, Ilaria Marigo, Sara Cingarlini, Luigi Dolcetti, Giovanna Gallina, Paola Zanovello & Vincenzo Bronte

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  1. Paolo Serafini
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  2. Carmela De Santo
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  3. Ilaria Marigo
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  8. Vincenzo Bronte
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Correspondence to Vincenzo Bronte.

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This article forms part of the Symposium in Writing “Inhibitors of immunosurveillance and anti-tumor immunity,” published in Vol. 53.

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Serafini, P., De Santo, C., Marigo, I. et al. Derangement of immune responses by myeloid suppressor cells. Cancer Immunol Immunother 53, 64–72 (2004). https://doi.org/10.1007/s00262-003-0443-2

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