Models of inflammatory processes in cancer

  • Roberto Benelli
  • Guido Frumento
  • Adriana Albini
  • Douglas M. Noonan
Part of the Progress in Inflammation Research book series (PIR)


A variety of models reflecting a multitude of mechanisms are bringing into focus the role of inflammation as both a driving force in carcinogenesis as well as a potential weapon to combat tumors. Further, these models now provide the basis for screening for molecules able to break to the pro-cancer chronic inflammation cycle and turn the tide against tumors.


Dextran Sodium Sulfate Arginase Activity Oral Squamous Cell Carcinoma Cell Corneal Neovascularization Immature Myeloid Cell 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357(9255): 539–545PubMedGoogle Scholar
  2. 2.
    Coussens LM, Werb Z (2001) Inflammatory cells and cancer: think different! J Exp Med 193(6): F23–26PubMedGoogle Scholar
  3. 3.
    Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917): 860–867PubMedGoogle Scholar
  4. 4.
    Balkwill F, Charles KA, Mantovani A (2005) Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 7(3): 211–217PubMedGoogle Scholar
  5. 5.
    Avogadri F, Martinoli C, Petrovska L, Chiodoni C, Transidico P, Bronte V, Longhi R, Colombo MP, Dougan G, Rescigno M (2005) Cancer immunotherapy based on killing of Salmonella-infected tumor cells. Cancer Res 65(9): 3920–3927PubMedGoogle Scholar
  6. 6.
    Couch M, Saunders JK, O’Malley BW, Jr., Pardoll D, Jaffee E (2003) Genetically engineered tumor cell vaccine in a head and neck cancer model. Laryngoscope 113(3):552–556PubMedGoogle Scholar
  7. 7.
    Graf MR, Prins RM, Hawkins WT, Merchant RE (2002) Irradiated tumor cell vaccine for treatment of an established glioma. I. Successful treatment with combined radiotherapy and cellular vaccination. Cancer Immunol Immunother 51(4): 179–189PubMedGoogle Scholar
  8. 8.
    Kusumoto M, Umeda S, Ikubo A, Aoki Y, Tawfik O, Oben R, Williamson S, Jewell W, Suzuki T (2001) Phase 1 clinical trial of irradiated autologous melanoma cells adenovirally transduced with human GM-CSF gene. Cancer Immunol Immunother 50(7):373–381PubMedGoogle Scholar
  9. 9.
    Kutzler MA, Weiner DB (2004) Developing DNA vaccines that call to dendritic cells. J Clin Invest 114(9): 1241–1244PubMedGoogle Scholar
  10. 10.
    Neville ME, Robb RJ, Popescu MC (2001) In situ vaccination against a non-immunogenic tumour using intratumoural injections of liposomal interleukin 2. Cytokine 16(6):239–250PubMedGoogle Scholar
  11. 11.
    Portielje JE, Kruit WH, Eerenberg AJ, Schuler M, Sparreboom A, Lamers CH, Gratama JW, Stoter G, Huber C, Hack CE (2005) Subcutaneous injection of interleukin 12 induces systemic inflammatory responses in humans: implications for the use of IL-12 as vaccine adjuvant. Cancer Immunol Immunother 54(1): 37–43PubMedGoogle Scholar
  12. 12.
    Wada A, Tada Y, Shimozato O, Takiguchi Y, Tatsumi K, Kuriyama T, Tagawa M (2005) Vaccination of apoptotic Fas ligand-expressing tumors decreased antitumor responses by enhanced production of immunosuppressive cytokines. AntiCancer Res 25(1A):299–303PubMedGoogle Scholar
  13. 13.
    Moldovan L, Moldovan NI (2005) Role of monocytes and macrophages in angiogenesis. EXS (94): 127–146PubMedGoogle Scholar
  14. 14.
    Blankenstein T (2004) The role of inflammation in tumour growth and tumour suppression. Novartis Found Symp 256: 205–210; discussion 210–214, 259–269PubMedGoogle Scholar
  15. 15.
    Kulbe H, Levinson NR, Balkwill F, Wilson JL (2004) The chemokine network in cancer-much more than directing cell movement. Int J Dev Biol 48(5–6): 489–496PubMedGoogle Scholar
  16. 16.
    Dvorak HF (1986) Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315(26): 1650–1659PubMedGoogle Scholar
  17. 17.
    Benelli R, Albini A, Noonan D (2003) Neutrophils and angiogenesis: potential initiators of the angiogenic cascade. Chem Immunol Allergy 83: 167–181PubMedGoogle Scholar
  18. 18.
    Scapini P, Morini M, Tecchio C, Minghelli S, Di Carlo E, Tanghetti E, Albini A, Lowell C, Berton G, Noonan DM, Cassatella MA (2004) CXCL1/macrophage inflammatory protein-2-induced angiogenesis in vivo is mediated by neutrophil-derived vascular endothelial growth factor-A. J Immunol 172(8): 5034–5040PubMedGoogle Scholar
  19. 19.
    Sparmann A, Bar-Sagi D (2004) Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell 6(5): 447–458PubMedGoogle Scholar
  20. 20.
    Karin M (2005) Inflammation and cancer: the long reach of Ras. Nat Med 11(1): 20–21PubMedGoogle Scholar
  21. 21.
    Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2(3): 161–174PubMedGoogle Scholar
  22. 22.
    Hayashido Y, Urabe K, Yoshioka Y, Kitano H, Okamoto T, Matsuya T (2003) Participation of fibroblasts in MMP-2 binding and activation on the surface of oral squamous cell carcinoma cells. Int J Oncol 22(3): 657–662PubMedGoogle Scholar
  23. 23.
    Boyd RS, Balkwill FR (1999) MMP-2 release and activation in ovarian carcinoma: the role of fibroblasts. Br J Cancer 80(3–4): 315–321PubMedGoogle Scholar
  24. 24.
    Gunther K, Leier J, Henning G, Dimmler A, Weissbach R, Hohenberger W, Forster R (2005) Prediction of lymph node metastasis in colorectal carcinoma by expression of chemokine receptor CCR7. Int J Cancer 116(5): 726–733PubMedGoogle Scholar
  25. 25.
    Strieter RM, Belperio JA, Phillips RJ, Keane MP (2004) Chemokines: angiogenesis and metastases in lung cancer. Novartis Found Symp 256: 173–184; discussion 184–188, 259–269PubMedGoogle Scholar
  26. 26.
    Wang J, Xi L, Gooding W, Godfrey TE, Ferris RL (2005) Chemokine receptors 6 and 7 identify a metastatic expression pattern in squamous cell carcinoma of the head and neck. Adv Otorhinolaryngol 62: 121–133PubMedGoogle Scholar
  27. 27.
    Pollard JW (2004) Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 4(1): 71–78PubMedGoogle Scholar
  28. 28.
    Brigati C, Noonan DM, Albini A, Benelli R (2002) Tumors and inflammatory infiltrates: friends or foes? Clin Exp Metastasis 19(3): 247–258PubMedGoogle Scholar
  29. 29.
    Harmey JH, Bucana CD, Lu W, Byrne AM, McDonnell S, Lynch C, Bouchier-Hayes D, Dong Z (2002) Lipopolysaccharide-induced metastatic growth is associated with increased angiogenesis, vascular permeability and tumor cell invasion. Int J Cancer 101(5): 415–422PubMedGoogle Scholar
  30. 30.
    Clark DA, Coker R (1998) Transforming growth factor-beta (TGF-beta). Int J Biochem Cell Biol 30(3): 293–298PubMedGoogle Scholar
  31. 31.
    Gold LI (1999) The role for transforming growth factor-beta (TGF-beta) in human cancer. Crit Rev Oncog 10(4): 303–360PubMedGoogle Scholar
  32. 32.
    Engle SJ, Hoying JB, Boivin GP, Ormsby I, Gartside PS, Doetschman T (1999) Transforming growth factor beta1 suppresses nonmetastatic colon cancer at an early stage of tumorigenesis. Cancer Res 159(14): 3379–3386Google Scholar
  33. 33.
    Li F, Cao Y, Townsend CM, Jr, Ko TC (2005) TGF-beta signaling in colon cancer cells. World J Surg 29(3): 306–311PubMedGoogle Scholar
  34. 34.
    Engle SJ, Ormsby I, Pawlowski S, Boivin GP, Croft J, Balish E, Doetschman T (2002) Elimination of colon cancer in germ-free transforming growth factor beta 1-deficient mice. Cancer Res 62(22): 6362–6366PubMedGoogle Scholar
  35. 35.
    Berg DJ, Davidson N, Kuhn R, Muller W, Menon S, Holland G, Thompson-Snipes L, Leach MW, Rennick D (1996) Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses. J Clin Invest 98(4): 1010–1020PubMedGoogle Scholar
  36. 36.
    Suzuki R, Kohno H, Sugie S, Tanaka T (2004) Sequential observations on the occurrence of preneoplastic and neoplastic lesions in mouse colon treated with azoxymethane and dextran sodium sulfate. Cancer Sci 95(9): 721–727PubMedGoogle Scholar
  37. 37.
    Suzuki R, Kohno H, Sugie S, Tanaka T (2005) Dose-dependent promoting effect of dextran sodium sulfate on mouse colon carcinogenesis initiated with azoxymethane. Histol Histopathol 20(2): 483–492PubMedGoogle Scholar
  38. 38.
    Andres PG, Beck PL, Mizoguchi E, Mizoguchi A, Bhan AK, Dawson T, Kuziel WA, Maeda N, MacDermott RP, Podolsky DK, Reinecker HC (2000) Mice with a selective deletion of the CC chemokine receptors 5 or 2 are protected from dextran sodium sulfate-mediated colitis: lack of CC chemokine receptor 5 expression results in a NK1.1+ lymphocyte-associated Th2-type immune response in the intestine. J Immunol 164(12):6303–6312PubMedGoogle Scholar
  39. 39.
    Tokuyama H, Ueha S, Kurachi M, Matsushima K, Moriyasu F, Blumberg RS, Kakimi K (2005) The simultaneous blockade of chemokine receptors CCR2, CCR5 and CXCR3 by a non-peptide chemokine receptor antagonist protects mice from dextran sodium sulfate-mediated colitis. Int Immunol 17(8):1023–1034PubMedGoogle Scholar
  40. 40.
    Folkman J (2002) Role of angiogenesis in tumor growth and metastasis. Semin Oncol 29(6 Suppl 16): 15–18PubMedGoogle Scholar
  41. 41.
    Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1): 57–70PubMedGoogle Scholar
  42. 42.
    Cassatella MA, Gasperini S, Russo MP (1997) Cytokine expression and release by neutrophils. Ann NY Acad Sci 832: 233–242PubMedGoogle Scholar
  43. 43.
    Scapini P, Lapinet-Vera JA, Gasperini S, Calzetti F, Bazzoni F, Cassatella MA (2000) The neutrophil as a cellular source of chemokines. Immunol Rev 177: 195–203PubMedGoogle Scholar
  44. 44.
    Ellis LM (2005) Bevacizumab. Nat Rev Drug Discov (Suppl): S8–9PubMedGoogle Scholar
  45. 45.
    Turini ME, DuBois RN (2002) Cyclooxygenase-2: a therapeutic target. Annu Rev Med 53: 35–57PubMedGoogle Scholar
  46. 46.
    Albini A, Noonan DM (2005) Rescuing COX-2 inhibitors from the waste bin. J Natl Cancer Inst 97(11): 859–860PubMedGoogle Scholar
  47. 47.
    Benelli R, Albini A (1999) In vitro models of angiogenesis: the use of Matrigel. Int J Biol Markers 14(4): 243–246PubMedGoogle Scholar
  48. 48.
    Winkler JD, Seed MP (1997) Angiogenesis in inflammatory disease. Inflamm Res 46(5):157–158PubMedGoogle Scholar
  49. 49.
    Winkler JD, Jackson JR, Fan TP, Seed MP (2004) Angiogenesis. Birkhäuser, BaselGoogle Scholar
  50. 50.
    Nguyen M, Shing Y, Folkman J (1994) Quantitation of angiogenesis and antiangiogenesis in the chick embryo chorioallantoic membrane. Microvasc Res 47(1): 31–40PubMedGoogle Scholar
  51. 51.
    Peek MJ, Norman TM, Morgan C, Markham R, Fraser IS (1988) The chick chorioallantoic membrane assay: an improved technique for the study of angiogenic activity. Exp Pathol 34(1): 35–40PubMedGoogle Scholar
  52. 52.
    Albini A, Fontanini G, Masiello L, Tacchetti C, Bigini D, Luzzi P, Noonan DM, Stetler-Stevenson WG (1994) Angiogenic potential in vivo by Kaposi’s sarcoma cell-free supernatants and HIV-1 tat product: inhibition of KS-like lesions by tissue inhibitor of metalloproteinase-2. AIDS 8(9): 1237–1944PubMedGoogle Scholar
  53. 53.
    Passaniti A, Taylor RM, Pili R, Guo Y, Long PV, Haney JA, Pauly RR, Grant DS, Martin GR (1992) A simple, quantitative method for assessing angiogenesis and antiangiogenic agents using reconstituted basement membrane, heparin, and fibroblast growth factor. Lab Invest 67(4): 519–528PubMedGoogle Scholar
  54. 54.
    Benelli R, Morini M, Carrozzino F, Ferrari N, Minghelli S, Santi L, Cassatella M, Noonan DM, Albini A (2002) Neutrophils as a key cellular target for angiostatin: implications for regulation of angiogenesis and inflammation. FASEB J 16(2): 267–269PubMedGoogle Scholar
  55. 55.
    Benelli R, Vene R, Bisacchi D, Garbisa S, Albini A (2002) Anti-invasive effects of green tea polyphenol epigallocatechin-3-gallate (EGCG), a natural inhibitor of metallo and serine proteases. Biol Chem 383(1): 101–105PubMedGoogle Scholar
  56. 56.
    Dona M, Dell’Aica I, Calabrese F, Benelli R, Morini M, Albini A, Garbisa S (2003) Neutrophil restraint by green tea: inhibition of inflammation, associated angiogenesis, and pulmonary fibrosis. J Immunol 170(8): 4335–4341PubMedGoogle Scholar
  57. 57.
    Kenyon BM, Voest EE, Chen CC, Flynn E, Folkman J, D’Amato RJ (1996) A model of angiogenesis in the mouse cornea. Invest Ophthalmol Vis Sci 37(8): 1625–1632PubMedGoogle Scholar
  58. 58.
    Ryu S, Albert DM (1979) Evaluation of tumor angiogenesis factor with the rabbit cornea model. Invest Ophthalmol Vis Sci 18(8): 831–841PubMedGoogle Scholar
  59. 59.
    Sunderkotter C, Beil W, Roth J, Sorg C (1991) Cellular events associated with inflammatory angiogenesis in the mouse cornea. Am J Pathol 138(4): 931–939PubMedGoogle Scholar
  60. 60.
    Hernandez-Pando R, De La Luz Streber M, Orozco H, Arriaga K, Pavon L, Al-Nakhli SA, Rook GA (1998) The effects of androstenediol and dehydroepiandrosterone on the course and cytokine profile of tuberculosis in BALB/c mice. Immunology 95(2):234–241PubMedGoogle Scholar
  61. 61.
    Hogaboam CM, Chensue SW, Steinhauser ML, Huffnagle GB, Lukacs NW, Strieter RM, Kunkel SL (1997) Alteration of the cytokine phenotype in an experimental lung granuloma model by inhibiting nitric oxide. J Immunol 159(11): 5585–5593PubMedGoogle Scholar
  62. 62.
    Frydas S, Papazahariadou M, Papaioannou N, Hatzistilianou M, Trakatellis M, Merlitti D, Di Gioacchino M, Grilli A, DeLutiis MA, Riccioni G et al (2003) Effect of the compound L-mimosine in an in vivo model of chronic granuloma formation induced by potassium permanganate (KMNO4). Int J Immunopathol Pharmacol 16(2): 99–104PubMedGoogle Scholar
  63. 63.
    Okada F, Kawaguchi T, Habelhah H, Kobayashi T, Tazawa H, Takeichi N, Kitagawa T, Hosokawa M (2000) Conversion of human colonic adenoma cells to adenocarcinoma cells through inflammation in nude mice. Lab Invest 80(11): 1617–1628PubMedGoogle Scholar
  64. 64.
    Rovere-Querini P, Capobianco A, Scaffidi P, Valentinis B, Catalanotti F, Giazzon M, Dumitriu IE, Muller S, Iannacone M, Traversari C et al (2004) HMGB1 is an endogenous immune adjuvant released by necrotic cells. EMBO Rep 5(8): 825–830PubMedGoogle Scholar
  65. 65.
    Sheikh AY, Rollins MD, Hopf HW, Hunt TK (2005) Hyperoxia improves microvascular perfusion in a murine wound model. Wound Repair Regen 13(3): 303–308PubMedGoogle Scholar
  66. 66.
    Lees VC, Fan TP (1994) A freeze-injured skin graft model for the quantitative study of basic fibroblast growth factor and other promoters of angiogenesis in wound healing. Br J Plast Surg 47(5): 349–359PubMedGoogle Scholar
  67. 67.
    Altavilla D, Galeano M, Bitto A, Minutoli L, Squadrito G, Seminara P, Venuti FS, Torre V, Calo M, Colonna M et al (2005) Lipid peroxidation inhibition by raxofelast improves angiogenesis and wound healing in experimental burn wounds. Shock 24(1): 85–91PubMedGoogle Scholar
  68. 68.
    Ciancio SJ, Coburn M, Hornsby PJ (2000) Cutaneous window for in vivo observations of organs and angiogenesis. J Surg Res 92(2): 228–232PubMedGoogle Scholar
  69. 69.
    Tettamanti G, Grimaldi A, Rinaldi L, Arnaboldi F, Congiu T, Valvassori R, de Eguileor M (2004) The multifunctional role of fibroblasts during wound healing in Hirudo medicinalis (Annelida, Hirudinea). Biol Cell 96(6): 443–455PubMedGoogle Scholar
  70. 70.
    Tettamanti G, Grimaldi A, Congiu T, Perletti G, Raspanti M, Valvassori R, de Eguileor M (2005) Collagen reorganization in leech wound healing. Biol Cell 97(7): 557–568PubMedGoogle Scholar
  71. 71.
    de Eguileor M, Tettamanti G, Grimaldi A, Perletti G, Congiu T, Rinaldi L, Valvassori R (2004) Hirudo medicinalis: avascular tissues for clear-cut angiogenesis studies? Curr Pharm Des 10(16): 1979–1988PubMedGoogle Scholar
  72. 72.
    Tettamanti G, Grimaldi A, Valvassori R, Rinaldi L, de Eguileor M (2003) Vascular endothelial growth factor is involved in neoangiogenesis in Hirudo medicinalis (Annelida, Hirudinea). Cytokine 22(6): 168–179PubMedGoogle Scholar
  73. 73.
    de Eguileor M, Tettamanti G, Grimaldi A, Congiu T, Ferrarese R, Perletti G, Valvassori R, Cooper EL, Lanzavecchia G (2003) Leeches: immune response, angiogenesis and biomedical applications. Curr Pharm Des 9(2): 133–147PubMedGoogle Scholar
  74. 74.
    de Eguileor M, Grimaldi A, Tettamanti G, Ferrarese R, Congiu T, Protasoni M, Perletti G, Valvassori R, Lanzavecchia G (2001) Hirudo medicinalis: a new model for testing activators and inhibitors of angiogenesis. Angiogenesis 4(4): 299–312PubMedGoogle Scholar
  75. 75.
    Bendall L (2005) Chemokines and their receptors in disease. Histol Histopathol 20(3): 907–926PubMedGoogle Scholar
  76. 76.
    Coelho AL, Hogaboam CM, Kunkel SL (2005) Chemokines provide the sustained inflammatory bridge between innate and acquired immunity. Cytokine Growth Factor Rev 16(6): 553–560PubMedGoogle Scholar
  77. 77.
    Kim CH (2005) The greater chemotactic network for lymphocyte trafficking: chemokines and beyond. Curr Opin Hematol 12(4): 298–304PubMedGoogle Scholar
  78. 78.
    Gerard C, Rollins BJ (2001) Chemokines and disease. Nat Immunol 2(2): 108–115PubMedGoogle Scholar
  79. 79.
    Nesbit M, Schaider H, Miller TH, Herlyn M (2001) Low-level monocyte chemoattractant protein-1 stimulation of monocytes leads to tumor formation in nontumorigenic melanoma cells. J Immunol 166(11): 6483–6490PubMedGoogle Scholar
  80. 80.
    Salcedo R, Ponce ML, Young HA, Wasserman K, Ward JM, Kleinman HK, Oppenheim JJ, Murphy WJ (2000) Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression. Blood 96(1): 34–40PubMedGoogle Scholar
  81. 81.
    Strieter RM, Belperio JA, Phillips RJ, Keane MP (2004) CXC chemokines in angiogenesis of cancer. Semin Cancer Biol 14(3): 195–200PubMedGoogle Scholar
  82. 82.
    Schaider H, Oka M, Bogenrieder T, Nesbit M, Satyamoorthy K, Berking C, Matsushima K, Herlyn M (2003) Differential response of primary and metastatic melanomas to neutrophils attracted by IL-8. Int J Cancer 103(3): 335–343PubMedGoogle Scholar
  83. 83.
    van Deventer HW, O’Connor W Jr, Brickey WJ, Aris RM, Ting JP, Serody JS (2005) CC chemokine receptor 5 on stromal cells promotes pulmonary metastasis. Cancer Res 65(8): 3374–3379PubMedGoogle Scholar
  84. 84.
    Ambati BK, Anand A, Joussen AM, Kuziel WA, Adamis AP, Ambati J (2003) Sustained inhibition of corneal neovascularization by genetic ablation of CCR5. Invest Ophthalmol Vis Sci 44(2): 590–593PubMedGoogle Scholar
  85. 85.
    Coussens LM, Raymond WW, Bergers G, Laig-Webster M, Behrendtsen O, Werb Z, Caughey GH, Hanahan D (1999) Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis. Genes Dev 13(11): 1382–1397PubMedGoogle Scholar
  86. 86.
    Daniel D, Meyer-Morse N, Bergsland EK, Dehne K, Coussens LM, Hanahan D (2003) Immune enhancement of skin carcinogenesis by CD4+ T cells. J Exp Med 197(8): 1017–1028PubMedGoogle Scholar
  87. 87.
    de Visser KE, Korets LV, Coussens LM (2005) De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Cancer Cell 7(5): 411–423PubMedGoogle Scholar
  88. 88.
    Mantovani A, Ming WJ, Balotta C, Abdeljalil B, Bottazzi B (1986) Origin and regulation of tumor-associated macrophages: the role of tumor-derived chemotactic factor. Biochim Biophys Acta 865(1): 59–67PubMedGoogle Scholar
  89. 89.
    Otsuji M, Kimura Y, Aoe T, Okamoto Y, Saito T (1996) Oxidative stress by tumorderived macrophages suppresses the expression of CD3 zeta chain of T-cell receptor complex and antigen-specific T-cell responses. Proc Natl Acad Sci USA 93(23): 13119–13124PubMedGoogle Scholar
  90. 90.
    Lewis CE, Leek R, Harris A, McGee JO (1995) Cytokine regulation of angiogenesis in breast cancer: the role of tumor-associated macrophages. J Leukoc Biol 57(5): 747–751PubMedGoogle Scholar
  91. 91.
    Yu JL, Rak JW (2003) Host microenvironment in breast cancer development: inflammatory and immune cells in tumour angiogenesis and arteriogenesis. Breast Cancer Res 5(2): 83–88PubMedGoogle Scholar
  92. 92.
    Chen JJ, Lin YC, Yao PL, Yuan A, Chen HY, Shun CT, Tsai MF, Chen CH, Yang PC (2005) Tumor-associated macrophages: the double-edged sword in cancer progression. J Clin Oncol 23(5): 953–964PubMedGoogle Scholar
  93. 93.
    Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M (2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25(12): 677–686PubMedGoogle Scholar
  94. 94.
    Sica A, Saccani A, Bottazzi B, Polentarutti N, Vecchi A, van Damme J, Mantovani A (2000) Autocrine production of IL-10 mediates defective IL-12 production and NFkappa B activation in tumor-associated macrophages. J Immunol 164(2): 762–767PubMedGoogle Scholar
  95. 95.
    Schmielau J, Finn OJ (2001) Activated granulocytes and granulocyte-derived hydrogen peroxide are the underlying mechanism of suppression of T-cell function in advanced cancer patients. Cancer Res 61(12): 4756–4760PubMedGoogle Scholar
  96. 96.
    Munder M, Mollinedo F, Calafat J, Canchado J, Gil-Lamaignere C, Fuentes JM, Luckner C, Doschko G, Soler G, Eichmann K et al (2005) Arginase I is constitutively expressed in human granulocytes and participates in fungicidal activity. Blood 105(6): 2549–2556PubMedGoogle Scholar
  97. 97.
    Zea AH, Rodriguez PC, Atkins MB, Hernandez C, Signoretti S, Zabaleta J, McDermott D, Quiceno D, Youmans A, O’Neill A et al (2005) Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion. Cancer Res 65(8): 3044–3048PubMedGoogle Scholar
  98. 98.
    Bronte V, Serafini P, De Santo C, Marigo I, Tosello V, Mazzoni A, Segal DM, Staib C, Lowel M, Sutter G et al (2003) IL-4-induced arginase 1 suppresses alloreactive T cells in tumor-bearing mice. J Immunol 170(1): 270–278PubMedGoogle Scholar
  99. 99.
    Zea AH, Rodriguez PC, Culotta KS, Hernandez CP, DeSalvo J, Ochoa JB, Park HJ, Zabaleta J, Ochoa AC (2004) L-Arginine modulates CD3zeta expression and T cell function in activated human T lymphocytes. Cell Immunol 232(1–2):21–31PubMedGoogle Scholar
  100. 100.
    Dvorak AM, Morgan ES, Tzizik DM, Weller PF (1994) Prostaglandin endoperoxide synthase (cyclooxygenase): ultrastructural localization to nonmembrane-bound cytoplasmic lipid bodies in human eosinophils and 3T3 fibroblasts. Int Arch Allergy Immunol 105(3): 245–250PubMedGoogle Scholar
  101. 101.
    Sousa A, Pfister R, Christie PE, Lane SJ, Nasser SM, Schmitz-Schumann M, Lee TH (1997) Enhanced expression of cyclo-oxygenase isoenzyme 2 (COX-2) in asthmatic airways and its cellular distribution in aspirin-sensitive asthma. Thorax 52(11): 940–945PubMedGoogle Scholar
  102. 102.
    Akasaki Y, Liu G, Chung NH, Ehtesham M, Black KL, Yu JS (2004) Induction of a CD4+ T regulatory type 1 response by cyclooxygenase-2-overexpressing glioma. J Immunol 173(7): 4352–4359PubMedGoogle Scholar
  103. 103.
    Munn DH, Shafizadeh E, Attwood JT, Bondarev I, Pashine A, Mellor AL (1999) Inhibition of T cell proliferation by macrophage tryptophan catabolism. J Exp Med 189(9): 1363–1372PubMedGoogle Scholar
  104. 104.
    Odemuyiwa SO, Ghahary A, Li Y, Puttagunta L, Lee JE, Musat-Marcu S, Ghahary A, Moqbel R (2004) Cutting edge: human eosinophils regulate T cell subset selection through indoleamine 2,3-dioxygenase. J Immunol 173(10): 5909–5913PubMedGoogle Scholar
  105. 105.
    Ratto GB, Zino P, Mirabelli S, Minuti P, Aquilina R, Fantino G, Spessa E, Ponte M, Bruzzi P, Melioli G (1996) A randomized trial of adoptive immunotherapy with tumorinfiltrating lymphocytes and interleukin-2 versus standard therapy in the postoperative treatment of resected nonsmall cell lung carcinoma. Cancer 78(2): 244–251PubMedGoogle Scholar
  106. 106.
    Sakaguchi S, Sakaguchi N, Shimizu J, Yamazaki S, Sakihama T, Itoh M, Kuniyasu Y, Nomura T, Toda M, Takahashi T (2001) Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol Rev 182: 18–32PubMedGoogle Scholar
  107. 107.
    Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10(9): 942–949PubMedGoogle Scholar
  108. 108.
    Kosaka T, Kuwabara M, Endo A, Tamaguchi H, Koide F (1991) Expression of arginase by mouse myeloid leukemic cell differentiation in vitro induced with tumor necrosis factor. J Vet Med Sci 53(1): 53–57PubMedGoogle Scholar
  109. 109.
    Kusmartsev S, Nefedova Y, Yoder D, Gabrilovich DI (2004) Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species. J Immunol 172(2): 989–999PubMedGoogle Scholar
  110. 110.
    Bozza S, Fallarino F, Pitzurra L, Zelante T, Montagnoli C, Bellocchio S, Mosci P, Vacca C, Puccetti P, Romani L (2005) A crucial role for tryptophan catabolism at the host/Candida albicans interface. J Immunol 174(5): 2910–2908PubMedGoogle Scholar
  111. 111.
    Thomas SR, Mohr D, Stocker R (1994) Nitric oxide inhibits indoleamine 2,3-dioxygenase activity in interferon-gamma primed mononuclear phagocytes. J Biol Chem 269(20): 14457–14464PubMedGoogle Scholar
  112. 112.
    Rodriguez PC, Zea AH, DeSalvo J, Culotta KS, Zabaleta J, Quiceno DG, Ochoa JB, Ochoa AC (2003) L-Arginine consumption by macrophages modulates the expression of CD3 zeta chain in T lymphocytes. J Immunol 171(3): 1232–1239PubMedGoogle Scholar
  113. 113.
    Huang MH, Yu CL, Han SH, Chiang BN, Wang SR (1990) Evidence that an immunosuppressive protein from murine liver is arginase. Biomed Biochim Acta 49(4): 179–187PubMedGoogle Scholar
  114. 114.
    Takikawa O, Kuroiwa T, Yamazaki F, Kido R (1988) Mechanism of interferon-gamma action. Characterization of indoleamine 2,3-dioxygenase in cultured human cells induced by interferon-gamma and evaluation of the enzyme-mediated tryptophan degradation in its anticellular activity. J Biol Chem 263(4): 2041–2048PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 2006

Authors and Affiliations

  • Roberto Benelli
    • 1
  • Guido Frumento
    • 1
  • Adriana Albini
    • 1
  • Douglas M. Noonan
    • 2
  1. 1.Dept of Translational OncologyIstituto Nazionale per la Ricerca sul CancroGenovaItaly
  2. 2.Dept of Clinical and Biological SciencesUniversity of InsubriaVareseItaly

Personalised recommendations