Macrophages and Tumor Development

  • Suzanne Ostrand-Rosenberg
  • Pratima Sinha


Nitric Oxide Vascular Endothelial Growth Factor Tumor Immunity Promote Tumor Progression Arginine Metabolism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Albina, J. E., Cui, S., Mateo, R. B., and Reichner, J. S. (1993). Nitric oxide-mediated apoptosis in murine peritoneal macrophages. J Immunol 150:5080–5085.PubMedGoogle Scholar
  2. Balkwill, F., Charles, K. A., and Mantovani, A. (2005). Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 7:211–217.PubMedCrossRefGoogle Scholar
  3. Balkwill, F., and Mantovani, A. (2001). Inflammation and cancer: back to Virchow? Lancet 357:539–545.PubMedCrossRefGoogle Scholar
  4. Barleon, B., Sozzani, S., Zhou, D., Weich, H. A., Mantovani, A., and Marme, D. (1996). Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. Blood 87:3336–3343.PubMedGoogle Scholar
  5. Becker, S., and Daniel, E. G. (1990). Antagonistic and additive effects of IL-4 and interferon-gamma on human monocytes and macrophages: effects on Fc receptors, HLA-D antigens, and superoxide production. Cell Immunol 129:351–362.PubMedCrossRefGoogle Scholar
  6. Bingle, L., Brown, N. J., and Lewis, C. E. (2002). The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol 196:254–265.PubMedCrossRefGoogle Scholar
  7. Bingle, L., Lewis, C. E., Corke, K. P., Reed, M. W., and Brown, N. J. (2006). Macrophages promote angiogenesis in human breast tumour spheroids in vivo. Br J Cancer 94:101–107.PubMedCrossRefGoogle Scholar
  8. Biswas, S. K., Gangi, L., Paul, S., Schioppa, T., Saccani, A., Sironi, M., Bottazzi, B., Doni, A., Vincenzo, B., Pasqualini, F., Vago, L., Nebuloni, M., Mantovani, A., and Sica, A. (2006). A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation). Blood 107:2112–2122.PubMedCrossRefGoogle Scholar
  9. Bogdan, C. (2001). Nitric oxide and the immune response. Nat Immunol 2:907–916.PubMedCrossRefGoogle Scholar
  10. Bonecchi, R., Sozzani, S., Stine, J. T., Luini, W., D’Amico, G., Allavena, P., Chantry, D., and Mantovani, A. (1998). Divergent effects of interleukin-4 and interferon-gamma on macrophage-derived chemokine production: an amplification circuit of polarized T helper 2 responses. Blood 92:2668–2671.PubMedGoogle Scholar
  11. Bosisio, D., Polentarutti, N., Sironi, M., Bernasconi, S., Miyake, K., Webb, G. R., Martin, M. U., Mantovani, A., and Muzio, M. (2002). Stimulation of toll-like receptor 4 expression in human mononuclear phagocytes by interferon-gamma: a molecular basis for priming and synergism with bacterial lipopolysaccharide. Blood 99:3427–3431.PubMedCrossRefGoogle Scholar
  12. Bowlin, T. L., McKown, B. J., and Sunkara, P. S. (1987). Increased ornithine decarboxylase activity and polyamine biosynthesis are required for optimal cytolytic T lymphocyte induction. Cell Immunol 105:110–117.PubMedCrossRefGoogle Scholar
  13. Bronte, V., Serafini, P., Mazzoni, A., Segal, D. M., and Zanovello, P. (2003). l-Arginine metabolism in myeloid cells controls T-lymphocyte functions. Trends Immunol 24: 302–306.PubMedCrossRefGoogle Scholar
  14. Bronte, V., and Zanovello, P. (2005). Regulation of immune responses by l-arginine metabolism. Nat Rev Immunol 5:641–654.PubMedCrossRefGoogle Scholar
  15. Brown, G. D., Taylor, P. R., Reid, D. M., Willment, J. A., Williams, D. L., Martinez-Pomares, L., Wong, S. Y., and Gordon, S. (2002). Dectin-1 is a major beta-glucan receptor on macrophages. J Exp Med 196:407–412.PubMedCrossRefGoogle Scholar
  16. Bunt, S. K., Sinha, P., Clements, V. K., Leips, J., and Ostrand-Rosenberg, S. (2006). Inflammation induces myeloid-derived suppressor cells that facilitate tumor progression. J Immunol 176:284–290.PubMedGoogle Scholar
  17. Burke, B., Tang, N., Corke, K. P., Tazzyman, D., Ameri, K., Wells, M., and Lewis, C. E. (2002). Expression of HIF-1alpha by human macrophages: implications for the use of macrophages in hypoxia-regulated cancer gene therapy. J Pathol 196:204–212.PubMedCrossRefGoogle Scholar
  18. Colombo, M. P., and Mantovani, A. (2005). Targeting myelomonocytyic cells to revert inflammatin-dependent cancer promotion. Cancer Res 65:9113–9116.PubMedCrossRefGoogle Scholar
  19. Coussens, L. M., and Werb, Z. (2002). Inflammation and cancer. Nature 420:860–867.PubMedCrossRefGoogle Scholar
  20. Dalton, D. K., Pitts-Meek, S., Keshav, S., Figari, I. S., Bradley, A., and Stewart, T. A. (1993). Multiple defects of immune cell function in mice with disrupted interferon-gamma genes. Science 259:1739–1742.PubMedCrossRefGoogle Scholar
  21. de Waal Malefyt, R., Figdor, C. G., Huijbens, R., Mohan-Peterson, S., Bennett, B., Culpepper, J., Dang, W., Zurawski, G., and de Vries, J. E. (1993). Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-gamma or IL-10. J Immunol 151:6370–6381.Google Scholar
  22. Elgert, K. D., Alleva, D. G., and Mullins, D. W. (1998). Tumor-induced immune dysfunction: the macrophage connection. J Leukoc Biol 64:275–290.PubMedGoogle Scholar
  23. Evans, R., and Alexander, P. (1972a). Role of macrophages in tumour immunity. I. Co-operation between macrophages and lymphoid cells in syngeneic tumour immunity. Immunology 23:615–626.Google Scholar
  24. Evans, R., and Alexander, P. (1972b). Role of macrophages in tumour immunity. II. Involvement of a macrophage cytophilic factor during syngeneic tumour growth inhibition. Immunology 23:627–636.Google Scholar
  25. Foekens, J. A., Peters, H. A., Look, M. P., Portengen, H., Schmitt, M., Kramer, M. D., Brunner, N., Janicke, F., Meijer-van Gelder, M. E., Henzen-Logmans, S. C., van Putten, W. L., and Klijn, J. G. (2000). The urokinase system of plasminogen activation and prognosis in 2780 breast cancer patients. Cancer Res 60:636–643.PubMedGoogle Scholar
  26. Fulton, A. M., Loveless, S. E., and Heppner, G. H. (1984). Mutagenic activity of tumor-associated macrophages in Salmonella typhimurium strains TA98 and TA 100. Cancer Res 44:4308–4311.PubMedGoogle Scholar
  27. Gabrilovich, D. I., Bronte, V., Chen, S. H., Colombo, M. P., Ochoa, A., Ostrand-Rosenberg, S., and Schreiber, H. (2007). The terminology issue for myeloid-derived suppressor cells. Cancer Res 67:425; author reply 426.Google Scholar
  28. Ghassabeh, G. H., De Baetselier, P., Brys, L., Noel, W., Van Ginderachter, J. A., Meerschaut, S., Beschin, A., Brombacher, F., and Raes, G. (2006). Identification of a common gene signature for type II cytokine-associated myeloid cells elicited in vivo in different pathologic conditions. Blood 108:575–583.PubMedCrossRefGoogle Scholar
  29. Gordon, S. (2003a). Alternative activation of macrophages. Nat Rev Immunol 3:23–35.CrossRefGoogle Scholar
  30. Gordon, S. (2003b). Macrophages and the immune response. Fundamental Immunology. W. Paul. Philadelphia: Lippincott-Raven Press, pp. 481–495.Google Scholar
  31. Gordon, S. (2006). Mononuclear phagocytes in immune defence. Immunology. I. Roitt, J. Brostoff, D. Male and D. Roth. Edinburgh: Mosby, pp. 148–162.Google Scholar
  32. Gordon, S., and Taylor, P. R. (2005). Monocyte and macrophage heterogeneity. Nat Rev Immunol 5:953–964.PubMedCrossRefGoogle Scholar
  33. Goswami, S., Sahai, E., Wyckoff, J. B., Cammer, M., Cox, D., Pixley, F. J., Stanley, E. R., Segall, J. E., and Condeelis, J. S. (2005). Macrophages promote the invasion of breast carcinoma cells via a colony-stimulating factor-1/epidermal growth factor paracrine loop. Cancer Res 65:5278–5283.PubMedCrossRefGoogle Scholar
  34. Greten, F. R., Eckmann, L., Greten, T. F., Park, J. M., Li, Z. W., Egan, L. J., Kagnoff, M. F., and Karin, M. (2004). IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118:285–296.PubMedCrossRefGoogle Scholar
  35. Griffiths, L., Binley, K., Iqball, S., Kan, O., Maxwell, P., Ratcliffe, P., Lewis, C., Harris, A., Kingsman, S., and Naylor, S. (2000). The macrophage—a novel system to deliver gene therapy to pathological hypoxia. Gene Ther 7:255–262.PubMedCrossRefGoogle Scholar
  36. Grimshaw, M. J., and Balkwill, F. R. (2001). Inhibition of monocyte and macrophage chemotaxis by hypoxia and inflammation—a potential mechanism. Eur J Immunol 31:480–489.PubMedCrossRefGoogle Scholar
  37. Grimshaw, M. J., Wilson, J. L., and Balkwill, F. R. (2002). Endothelin-2 is a macrophage chemoattractant: implications for macrophage distribution in tumors. Eur J Immunol 32:2393–2400.PubMedCrossRefGoogle Scholar
  38. Grohmann, U., Fallarino, F., and Puccetti, P. (2003). Tolerance, DCs and tryptophan: much ado about IDO. Trends Immunol 24:242–248.PubMedCrossRefGoogle Scholar
  39. Gu, L., Tseng, S., Horner, R. M., Tam, C., Loda, M., and Rollins, B. J. (2000). Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1. Nature 404:407–411.PubMedCrossRefGoogle Scholar
  40. Guiducci, C., Vicari, A. P., Sangaletti, S., Trinchieri, G., and Colombo, M. P. (2005). Redirecting in vivo elicited tumor infiltrating macrophages and dendritic cells towards tumor rejection. Cancer Res 65:3437–3446.PubMedGoogle Scholar
  41. Hagemann, T., Robinson, S. C., Schulz, M., Trumper, L., Balkwill, F. R., and Binder, C. (2004). Enhanced invasiveness of breast cancer cell lines upon co-cultivation with macrophages is due to TNF-alpha dependent up-regulation of matrix metalloproteases. Carcinogenesis 25: 1543–1549.PubMedCrossRefGoogle Scholar
  42. Heinzel, F. P., Sadick, M. D., Holaday, B. J., Coffman, R. L., and Locksley, R. M. (1989). Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J Exp Med 169:59–72.PubMedCrossRefGoogle Scholar
  43. Hildenbrand, R., Dilger, I., Horlin, A., and Stutte, H. J. (1995). Urokinase and macrophages in tumour angiogenesis. Br J Cancer 72:818–823.PubMedGoogle Scholar
  44. Imai, T., Nagira, M., Takagi, S., Kakizaki, M., Nishimura, M., Wang, J., Gray, P. W., Matsushima, K., and Yoshie, O. (1999). Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine. Int Immunol 11:81–88.PubMedCrossRefGoogle Scholar
  45. Jung, Y. J., Isaacs, J. S., Lee, S., Trepel, J., and Neckers, L. (2003). IL-1beta-mediated up-regulation of HIF-1alpha via an NFkappaB/COX-2 pathway identifies HIF-1 as a critical link between inflammation and oncogenesis. FASEB J 17:2115–2117.PubMedGoogle Scholar
  46. Kambayashi, T., Jacob, C. O., and Strassmann, G. (1996). IL-4 and IL-13 modulate IL-10 release in endotoxin-stimulated murine peritoneal mononuclear phagocytes. Cell Immunol 171:153–158.PubMedCrossRefGoogle Scholar
  47. Karin, M., and Greten, F. R. (2005). NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 5:749–759.PubMedCrossRefGoogle Scholar
  48. Karin, M., and Lin, A. (2002). NF-kappaB at the crossroads of life and death. Nat Immunol 3: 221–227.PubMedCrossRefGoogle Scholar
  49. Koide, Y., and Yoshida, A. (1994). The signal transduction mechanism responsible for gamma interferon-induced indoleamine 2,3-dioxygenase gene expression. Infect Immun 62:948–955.PubMedGoogle Scholar
  50. Koppenol, W. H., Moreno, J. J., Pryor, W. A., Ischiropoulos, H., and Beckman, J. S. (1992). Peroxynitrite, a cloaked oxidant formed by nitric oxide and superoxide. Chem Res Toxicol 5:834–842.PubMedCrossRefGoogle Scholar
  51. Kristiansen, M., Graversen, J. H., Jacobsen, C., Sonne, O., Hoffman, H. J., Law, S. K., and Moestrup, S. K. (2001). Identification of the haemoglobin scavenger receptor. Nature 409: 198–201.PubMedCrossRefGoogle Scholar
  52. Kusmartsev, S., and Gabrilovich, D. I. (2005). STAT1 signaling regulates tumor-associated macrophage-mediated T cell deletion. J Immunol 174:4880–4891.PubMedGoogle Scholar
  53. Kusmartsev, S., Nagaraj, S., and Gabrilovich, D. I. (2005). Tumor-associated CD8+ T cell tolerance induced by bone marrow-derived immature myeloid cells. J Immunol 175:4583–4592.PubMedGoogle Scholar
  54. Kusmartsev, S., Nefedova, Y., Yoder, D., and Gabrilovich, D. I. (2004). Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species. J Immunol 172:989–999.PubMedGoogle Scholar
  55. Lahat, N., Rahat, M. A., Ballan, M., Weiss-Cerem, L., Engelmayer, M., and Bitterman, H. (2003). Hypoxia reduces CD80 expression on monocytes but enhances their LPS-stimulated TNF-alpha secretion. J Leukoc Biol 74:197–205.PubMedCrossRefGoogle Scholar
  56. Lee, C. G., Homer, R. J., Zhu, Z., Lanone, S., Wang, X., Koteliansky, V., Shipley, J. M., Gotwals, P., Noble, P., Chen, Q., Senior, R. M., and Elias, J. A. (2001). Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta(1). J Exp Med 194:809–821.PubMedCrossRefGoogle Scholar
  57. Leek, R. D., Hunt, N. C., Landers, R. J., Lewis, C. E., Royds, J. A., and Harris, A. L. (2000). Macrophage infiltration is associated with VEGF and EGFR expression in breast cancer. J Pathol 190:430–436.PubMedCrossRefGoogle Scholar
  58. Leek, R. D., Lewis, C. E., Whitehouse, R., Greenall, M., Clarke, J., and Harris, A. L. (1996). Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res 56:4625–4629.PubMedGoogle Scholar
  59. Lewis, C., and Murdoch, C. (2005). Macrophage responses to hypoxia: implications for tumor progression and anti-cancer therapies. Am J Pathol 167:627–635.PubMedGoogle Scholar
  60. Lewis, C. E., and Pollard, J. W. (2006). Distinct role of macrophages in different tumor microenvironments. Cancer Res 66:605–612.PubMedCrossRefGoogle Scholar
  61. Lewis, J. S., Landers, R. J., Underwood, J. C., Harris, A. L., and Lewis, C. E. (2000). Expression of vascular endothelial growth factor by macrophages is up-regulated in poorly vascularized areas of breast carcinomas. J Pathol 192:150–158.PubMedCrossRefGoogle Scholar
  62. Lin, E. Y., Li, J. F., Gnatovskiy, L., Deng, Y., Zhu, L., Grzesik, D. A., Qian, H., Xue, X. N., and Pollard, J. W. (2006). Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res 66:11238–11246.PubMedCrossRefGoogle Scholar
  63. Lin, E. Y., Nguyen, A. V., Russell, R. G., and Pollard, J. W. (2001). Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med 193:727–740.PubMedCrossRefGoogle Scholar
  64. Luo, Y., Zhou, H., Krueger, J., Kaplan, C., Lee, S. H., Dolman, C., Markowitz, D., Wu, W., Liu, C., Reisfeld, R. A., and Xiang, R. (2006). Targeting tumor-associated macrophages as a novel strategy against breast cancer. J Clin Invest 116:2132–2141.PubMedCrossRefGoogle Scholar
  65. Mackaness, G. B. (1964). The immunological basis of acquired cellular resistance. J Exp Med 120:105–120.PubMedCrossRefGoogle Scholar
  66. MacMicking, J., Xie, Q. W., and Nathan, C. (1997). Nitric oxide and macrophage function. Annu Rev Immunol 15:323–350.PubMedCrossRefGoogle Scholar
  67. Maeda, H., and Akaike, T. (1998). Nitric oxide and oxygen radicals in infection, inflammation, and cancer. Biochemistry (Mosc) 63:854–865.Google Scholar
  68. Mantovani, A. (2005). Cancer: inflammation by remote control. Nature 435:752–753.PubMedCrossRefGoogle Scholar
  69. Mantovani, A. (2006). Macrophage diversity and polarization: in vivo veritas. Blood 108:408–409.CrossRefGoogle Scholar
  70. Mantovani, A., Locati, M., Vecchi, A., Sozzani, S., and Allavena, P. (2001). Decoy receptors: a strategy to regulate inflammatory cytokines and chemokines. Trends Immunol 22:328–336.PubMedCrossRefGoogle Scholar
  71. Mantovani, A., Schioppa, T., Porta, C., Allavena, P., and Sica, A. (2006). Role of tumor-associated macrophages in tumor progression and invasion. Cancer Metastasis Rev 25:315–322.PubMedCrossRefGoogle Scholar
  72. Mantovani, A., Sica, A., and Locati, M. (2005). Macrophage polarization comes of age. Immunity 23:344–346.PubMedCrossRefGoogle Scholar
  73. Mantovani, A., Sica, A., and Locati, M. (2007). New vistas on macrophage differentiation and activation. Eur J Immunol 37:14–16.PubMedCrossRefGoogle Scholar
  74. Mantovani, A., Sica, A., Sozzani, S., Allavena, P., Vecchi, A., and Locati, M. (2004). The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25:677–686.PubMedCrossRefGoogle Scholar
  75. Mantovani, A., Sozzani, S., Locati, M., Allavena, P., and Sica, A. (2002). Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23:549–555.PubMedCrossRefGoogle Scholar
  76. Metchnikoff, E. (1905). Immunity in infective disease. Cambridge: Cambridge University Press.Google Scholar
  77. Mills, C. D. (2001). Macrophage arginine metabolism to ornithine/urea or nitric oxide/citrulline: a life or death issue. Crit Rev Immunol 21:399–425.PubMedGoogle Scholar
  78. Mills, C. D., Kincaid, K., Alt, J. M., Heilman, M. J., and Hill, A. M. (2000). M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol 164:6166–6173.PubMedGoogle Scholar
  79. Morris, S. M., Jr, Kepka-Lenhart, D., and Chen, L. C. (1998). Differential regulation of arginases and inducible nitric oxide synthase in murine macrophage cells. Am J Physiol 275:E740–E747.Google Scholar
  80. Mosmann, T. R., and Coffman, R. L. (1989). TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 7:145–173.PubMedCrossRefGoogle Scholar
  81. Mosmann, T. R., and Sad, S. (1996). The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 17:138–146.PubMedCrossRefGoogle Scholar
  82. Munn, D. H., and Mellor, A. L. (2004). IDO and tolerance to tumors. Trends Mol Med 10:15–18.PubMedCrossRefGoogle Scholar
  83. Munn, D. H., and Mellor, A. L. (2006). The tumor-draining lymph node as an immune-privileged site. Immunol Rev 213:146–158.PubMedCrossRefGoogle Scholar
  84. Munn, D. H., Shafizadeh, E., Attwood, J. T., Bondarev, I., Pashine, A., and Mellor, A. L. (1999). Inhibition of T cell proliferation by macrophage tryptophan catabolism. J Exp Med 189: 1363–1372.PubMedCrossRefGoogle Scholar
  85. Murdoch, C., and Lewis, C. E. (2005). Macrophage migration and gene expression in response to tumor hypoxia. Int J Cancer 117:701–708.PubMedCrossRefGoogle Scholar
  86. Murdoch, C., Muthana, M., and Lewis, C. E. (2005). Hypoxia regulates macrophage functions in inflammation. J Immunol 175:6257–6263.PubMedGoogle Scholar
  87. Nathan, C. F., and Hibbs, J. B., Jr (1991). Role of nitric oxide synthesis in macrophage antimicrobial activity. Curr Opin Immunol 3:65–70.PubMedCrossRefGoogle Scholar
  88. Negus, R. P., Stamp, G. W., Hadley, J., and Balkwill, F. R. (1997). Quantitative assessment of the leukocyte infiltrate in ovarian cancer and its relationship to the expression of C–C chemokines. Am J Pathol 150:1723–1734.PubMedGoogle Scholar
  89. Ogawa, K., Funaba, M., Chen, Y., and Tsujimoto, M. (2006). Activin A functions as a Th2 cytokine in the promotion of the alternative activation of macrophages. J Immunol 177:6787–6794.PubMedGoogle Scholar
  90. O’Sullivan, C., Lewis, C. E., Harris, A. L., and McGee, J. O. (1993). Secretion of epidermal growth factor by macrophages associated with breast carcinoma. Lancet 342:148–149.PubMedCrossRefGoogle Scholar
  91. Pegg, A. E. (1988). Polyamine metabolism and its importance in neoplastic growth and a target for chemotherapy. Cancer Res 48:759–774.PubMedGoogle Scholar
  92. Pesce, J., Kaviratne, M., Ramalingam, T. R., Thompson, R. W., Urban, J. F., Jr, Cheever, A. W., Young, D. A., Collins, M., Grusby, M. J., and Wynn, T. A. (2006). The IL-21 receptor augments Th2 effector function and alternative macrophage activation. J Clin Invest 116:2044–2055.PubMedCrossRefGoogle Scholar
  93. Pikarsky, E., Porat, R. M., Stein, I., Abramovitch, R., Amit, S., Kasem, S., Gutkovich-Pyest, E., Urieli-Shoval, S., Galun, E., and Ben-Neriah, Y. (2004). NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 431:461–466.PubMedCrossRefGoogle Scholar
  94. Pollard, J. W. (2004). Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 4:71–78.PubMedCrossRefGoogle Scholar
  95. Rauh, M. J., Ho, V., Pereira, C., Sham, A., Sly, L. M., Lam, V., Huxham, L., Minchinton, A. I., Mui, A., and Krystal, G. (2005). SHIP represses the generation of alternatively activated macrophages. Immunity 23:361–374.PubMedCrossRefGoogle Scholar
  96. Rissoan, M. C., Soumelis, V., Kadowaki, N., Grouard, G., Briere, F., de Waal Malefyt, R., and Liu, Y. J. (1999). Reciprocal control of T helper cell and dendritic cell differentiation. Science 283:1183–1186.PubMedCrossRefGoogle Scholar
  97. Rodriguez, P. C., Hernandez, C. P., Quiceno, D., Dubinett, S. M., Zabaleta, J., Ochoa, J. B., Gilbert, J., and Ochoa, A. C. (2005). Arginase I in myeloid suppressor cells is induced by COX-2 in lung carcinoma. J Exp Med 202:931–939.PubMedCrossRefGoogle Scholar
  98. Rodriguez, P. C., and Ochoa, A. C. (2006). T cell dysfunction in cancer: role of myeloid cells and tumor cells regulating amino acid availability and oxidative stress. Semin Cancer Biol 16:66–72.PubMedCrossRefGoogle Scholar
  99. Saccani, A., Schioppa, T., Porta, C., Biswas, S. K., Nebuloni, M., Vago, L., Bottazzi, B., Colombo, M. P., Mantovani, A., and Sica, A. (2006). p50 nuclear factor-kappaB overexpression in tumor-associated macrophages inhibits M1 inflammatory responses and antitumor resistance. Cancer Res 66:11432–11440.PubMedCrossRefGoogle Scholar
  100. Saio, M., Radoja, S., Marino, M., and Frey, A. B. (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 167:5583–5593.PubMedGoogle Scholar
  101. Scott, P., Natovitz, P., Coffman, R. L., Pearce, E., and Sher, A. (1988). Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens. J Exp Med 168: 1675–1684.PubMedCrossRefGoogle Scholar
  102. Seymour, R. L., Ganapathy, V., Mellor, A. L., and Munn, D. H. (2006). A high-affinity, tryptophan-selective amino acid transport system in human macrophages. J Leukoc Biol 80: 1320–1327.PubMedCrossRefGoogle Scholar
  103. Sica, A., and Bronte, V. (2007). Altered macrophage differentiation and immune dysfunction in tumor development. J Clin Invest 117:1155–1166.PubMedCrossRefGoogle Scholar
  104. Sica, A., Schioppa, T., Mantovani, A., and Allavena, P. (2006). Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer 42:717–727.PubMedCrossRefGoogle Scholar
  105. Siegert, A., Denkert, C., Leclere, A., and Hauptmann, S. (1999). Suppression of the reactive oxygen intermediates production of human macrophages by colorectal adenocarcinoma cell lines. Immunology 98:551–556.PubMedCrossRefGoogle Scholar
  106. Sinha, P., Bunt, S., Clements, V. K., Albelda, S., and Ostrand-Rosenberg, S. (2007a). Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity towards a type 2 response. J Immunol 179(2):977–83.Google Scholar
  107. Sinha, P., Clements, V. K., Fulton, A. M., and Ostrand-Rosenberg, S. (2007b). Prostaglandin E2 promotes tumor progression by inducing myeloid-derived suppressor cells. Cancer Res 67:4507–4513.CrossRefGoogle Scholar
  108. Sinha, P., Clements, V. K., and Ostrand-Rosenberg, S. (2005a). Interleukin-13-regulated M2 macrophages in combination with myeloid suppressor cells block immune surveillance against metastasis. Cancer Res 65:11743–11751.CrossRefGoogle Scholar
  109. Sinha, P., Clements, V. K., and Ostrand-Rosenberg, S. (2005b). Reduction of myeloid-derived suppressor cells and induction of M1 macrophages facilitate the rejection of established metastatic disease. J Immunol 174:636–645.Google Scholar
  110. Song, X., Krelin, Y., Dvorkin, T., Bjorkdahl, O., Segal, S., Dinarello, C. A., Voronov, E., and Apte, R. N. (2005). CD11b+/Gr-1+ immature myeloid cells mediate suppression of T cells in mice bearing tumors of IL-1beta-secreting cells. J Immunol 175:8200–8208.PubMedGoogle Scholar
  111. Stein, M., Keshav, S., Harris, N., and Gordon, S. (1992). Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation. J Exp Med 176:287–292.PubMedCrossRefGoogle Scholar
  112. Sun, B., Nishihira, J., Yoshiki, T., Kondo, M., Sato, Y., Sasaki, F., and Todo, S. (2005). Macrophage migration inhibitory factor promotes tumor invasion and metastasis via the Rho-dependent pathway. Clin Cancer Res 11:1050–1058.PubMedGoogle Scholar
  113. Talks, K. L., Turley, H., Gatter, K. C., Maxwell, P. H., Pugh, C. W., Ratcliffe, P. J., and Harris, A. L. (2000). The expression and distribution of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages. Am J Pathol 157:411–421.PubMedGoogle Scholar
  114. Tauber, A. I., and Chernyak, L. (1991). Metchnikoff and the Origins of Immunology: From Metaphor to Theory. New York: Oxford University Press.Google Scholar
  115. Taylor, P. R., and Gordon, S. (2003). Monocyte heterogeneity and innate immunity. Immunity 19:2–4.PubMedCrossRefGoogle Scholar
  116. Taylor, P. R., Martinez-Pomares, L., Stacey, M., Lin, H. H., Brown, G. D., and Gordon, S. (2005). Macrophage receptors and immune recognition. Annu Rev Immunol 23:901–944.PubMedCrossRefGoogle Scholar
  117. Terabe, M., Matsui, S., Noben-Trauth, N., Chen, H., Watson, C., Donaldson, D. D., Carbone, D. P., Paul, W. E., and Berzofsky, J. A. (2000). NKT cell-mediated repression of tumor immunosurveillance by IL-13 and the IL-4R-STAT6 pathway. Nat Immunol 1:515–520.PubMedCrossRefGoogle Scholar
  118. Terabe, M., Matsui, S., Park, J. M., Mamura, M., Noben-Trauth, N., Donaldson, D. D., Chen, W., Wahl, S. M., Ledbetter, S., Pratt, B., Letterio, J. J., Paul, W. E., and Berzofsky, J. A. (2003). Transforming growth factor-beta 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 198:1741–1752.PubMedCrossRefGoogle Scholar
  119. Tohyama, M., Kawakami, K., Futenma, M., and Saito, A. (1996). Enhancing effect of oxygen radical scavengers on murine macrophage anticryptococcal activity through production of nitric oxide. Clin Exp Immunol 103:436–441.PubMedCrossRefGoogle Scholar
  120. White, J. R., Harris, R. A., Lee, S. R., Craigon, M. H., Binley, K., Price, T., Beard, G. L., Mundy, C. R., and Naylor, S. (2004). Genetic amplification of the transcriptional response to hypoxia as a novel means of identifying regulators of angiogenesis. Genomics 83:1–8.PubMedCrossRefGoogle Scholar
  121. Wu, G., and Morris, S. M., Jr (1998). Arginine metabolism: nitric oxide and beyond. Biochem J 336(Pt 1):1–17.PubMedGoogle Scholar
  122. Wyckoff, J. B., Segall, J. E., and Condeelis, J. S. (2000). The collection of the motile population of cells from a living tumor. Cancer Res 60:5401–5404.PubMedGoogle Scholar
  123. Wyckoff, J. B., Wang, Y., Lin, E. Y., Li, J. F., Goswami, S., Stanley, E. R., Segall, J. E., Pollard, J. W., and Condeelis, J. (2007). Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Res 67:2649–2656.PubMedCrossRefGoogle Scholar
  124. Yang, L., DeBusk, L. M., Fukuda, K., Fingleton, B., Green-Jarvis, B., Shyr, Y., Matrisian, L. M., Carbone, D. P., and Lin, P. C. (2004). Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell 6:409–421.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Suzanne Ostrand-Rosenberg
    • 1
  • Pratima Sinha
  1. 1.Department of Biological SciencesUniversity of Maryland Baltimore CountyBaltimoreUSA

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