Glioma pp 53-76

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 746)

Mechanisms of Immune Evasion by Gliomas

  • Cleo E. Rolle
  • Sadhak Sengupta
  • Maciej S. Lesniak

Abstract

A major contributing factor to glioma development and progression is its ability to evade the immune system. This chapter will explore the mechanisms utilized by glioma to mediate immunosuppression and immune evasion. These include intrinsic mechanisms linked to its location within the brain and interactions between glioma cells and immune cells. Lack of recruitment of naïve effector immune cells perhaps accounts for most of the immune suppression mediated by these tumor cells. This is enhanced by increased recruitment of microglia which resemble immature antigen presenting cells that are unable to support T-cell mediated immunity. Furthermore, secreted factors like TGF-β, COX-2 and IL-10, altered costimulatory molecules and inhibition of STAT-3 all contribute to the recruitment and expansion of regulatory T cells, which further modulate the immunosuppressive environment of glioma. In light of these findings, multiple immunotherapeutic treatment modalities are currently being explored.

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References

  1. 1.
    Medawar PB. Immunity to homologous grafted skin; the fate of skin homografts transplanted to the brain, to subcutaneous tissue and to the anterior chamber of the eye. Br J Exp Pathol 1948; 29:58–69.PubMedGoogle Scholar
  2. 2.
    Freed WJ, Dymecki J, Poltorak M et al. Intraventricular brain allografts and xenografts: studies of survival and rejection with and without systemic sensitization. Prog Brain Res 1988; 78:233–241.PubMedCrossRefGoogle Scholar
  3. 3.
    Tsugawa T, Kuwashima N, Sato H et al. Sequential delivery of interferon-alpha gene and DCs to intracranial gliomas promotes an effective antitumor response. Gene Ther 2004; 11:1551–1558.PubMedCrossRefGoogle Scholar
  4. 4.
    El Andaloussi A, Lesniak MS. An increase in CD4+CD25+FOXP3+ regulatory T-cells in tumor-infiltrating lymphocytes of human glioblastoma multiforme. Neuro Oncol 2006; 8:234–243.PubMedCrossRefGoogle Scholar
  5. 5.
    El Andaloussi A, Han Y, Lesniak MS. Prolongation of survival following depletion of CD4+CD25+ regulatory T-cells in mice with experimental brain tumors. J Neurosurg 2006; 105:430–437.PubMedCrossRefGoogle Scholar
  6. 6.
    Fecci PE, Mitchell DA, Whitesides JF et al. Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma. Cancer Res 2006; 66:3294–3302.PubMedCrossRefGoogle Scholar
  7. 7.
    Heimberger AB, Abou-Ghazal M, Reina-Ortiz C et al. Incidence and prognostic impact of FoxP3+ regulatory T-cells in human gliomas. Clin Cancer Res 2008; 14:5166–5172.PubMedCrossRefGoogle Scholar
  8. 8.
    Facoetti A, Nano R, Zelini P et al. Human leukocyte antigen and antigen processing machinery component defects in astrocytic tumors. Clin Cancer Res 2005; 11:8304–8311.PubMedCrossRefGoogle Scholar
  9. 9.
    Mehling M, Simon P, Mittelbronn M et al. WHO grade associated downregulation of MHC class I antigen-processing machinery components in human astrocytomas: does it reflect a potential immune escape mechanism? Acta Neuropathol 2007; 114:111–119.PubMedCrossRefGoogle Scholar
  10. 10.
    Zuber P, Kuppner MC, De Tribolet N. Transforming growth factor-beta 2 down-regulates HLA-DR antigen expression on human malignant glioma cells. Eur J Immunol 1988; 18:1623–1626.PubMedCrossRefGoogle Scholar
  11. 11.
    Rossi ML, Esiri MM, Jones NR et al. Characterization of the mononuclear cell infiltrate and HLA-Dr expression in 19 oligodendrogliomas. Surg Neurol 1991; 36:119–125.PubMedCrossRefGoogle Scholar
  12. 12.
    Rossi ML, Jones NR, Karr GF et al. HLA-Dr expression by tumor cells compared with survival in high grade astrocytomas. Tumori 1991; 77:122–125.PubMedGoogle Scholar
  13. 13.
    Mouillot G, Marcou C, Rousseau P et al. HLA-G gene activation in tumor cells involves cis-acting epigenetic changes. Int J Cancer 2005; 113:928–936.PubMedCrossRefGoogle Scholar
  14. 14.
    Rebmann V, Regel J, Stolke D et al. Secretion of sHLA-G molecules in malignancies. Semin Cancer Biol 2003; 13:371–377.PubMedCrossRefGoogle Scholar
  15. 15.
    Pistoia V, Morandi F, Wang X et al. Soluble HLA-G: Are they clinically relevant? Semin Cancer Biol 2007; 17:469–479.PubMedCrossRefGoogle Scholar
  16. 16.
    Wiendl H, Mitsdoerffer M, Hofmeister V et al. A functional role of HLA-G expression in human gliomas: an alternative strategy of immune escape. J Immunol 2002; 168:4772–4780.PubMedGoogle Scholar
  17. 17.
    Wischhusen J, Friese MA, Mittelbronn M et al. HLA-E protects glioma cells from NKG2D-mediated immune responses in vitro: implications for immune escape in vivo. J Neuropathol Exp Neurol 2005; 64:523–528.PubMedGoogle Scholar
  18. 18.
    Mittelbronn M, Simon P, Loffler C et al. Elevated HLA-E levels in human glioblastomas but not in grade I to III astrocytomas correlate with infiltrating CD8+ cells. J Neuroimmunol 2007; 189:50–58.PubMedCrossRefGoogle Scholar
  19. 19.
    Guillemin GJ, Brew BJ. Microglia, macrophages, perivascular macrophages and pericytes: a review of function and identification. J Leukoc Biol 2004; 75:388–397.PubMedCrossRefGoogle Scholar
  20. 20.
    Penfield W. Microglia and the process of phagocytosis in gliomas. Am J Path 1925; 1:77–97.PubMedGoogle Scholar
  21. 21.
    Rossi ML, Hughes JT, Esiri MM et al. Immunohistological study of mononuclear cell infiltrate in malignant gliomas. Acta Neuropathol 1987; 74:269–277.PubMedCrossRefGoogle Scholar
  22. 22.
    Rossi ML, Jones NR, Candy E et al. The mononuclear cell infiltrate compared with survival in high-grade astrocytomas. Acta Neuropathol 1989; 78:189–193.PubMedCrossRefGoogle Scholar
  23. 23.
    Parney IF, Waldron JS, Parsa AT. Flow cytometry and in vitro analysis of human glioma-associated macrophages. J Neurosurg. 2009 Mar;110(3):572–82.PubMedCrossRefGoogle Scholar
  24. 24.
    Roggendorf W, Strupp S, Paulus W. Distribution and characterization of microglia/macrophages in human brain tumors. Acta Neuropathol 1996; 92:288–293.PubMedCrossRefGoogle Scholar
  25. 25.
    Leung SY, Wong MP, Chung LP et al. Monocyte chemoattractant protein-1 expression and macrophage infiltration in gliomas. Acta Neuropathol 1997; 93:518–527.PubMedCrossRefGoogle Scholar
  26. 26.
    Platten M, Kretz A, Naumann U et al. Monocyte chemoattractant protein-1 increases microglial infiltration and aggressiveness of gliomas. Ann Neurol 2003; 54:388–392.PubMedCrossRefGoogle Scholar
  27. 27.
    Aloisi F, Ria F, Penna G et al. Microglia are more efficient than astrocytes in antigen processing and in Th1 but not Th2 cell activation. J Immunol 1998; 160:4671–4680.PubMedGoogle Scholar
  28. 28.
    Flugel A, Labeur MS, Grasbon-Frodl EM et al. Microglia only weakly present glioma antigen to cytotoxic T-cells. Int J Dev Neurosci 1999; 17:547–556.PubMedCrossRefGoogle Scholar
  29. 29.
    Hussain SF, Yang D, Suki D et al. The role of human glioma-infiltrating microglia/macrophages in mediating antitumor immune responses. Neuro Oncol 2006; 8:261–279.PubMedCrossRefGoogle Scholar
  30. 30.
    Huettner C, Paulus W, Roggendorf W. Messenger RNA expression of the immunosuppressive cytokine IL-10 in human gliomas. Am J Pathol 1995; 146:317–322.PubMedGoogle Scholar
  31. 31.
    Goswami S, Gupta A, Sharma SK. Interleukin-6-mediated autocrine growth promotion in human glioblastoma multiforme cell line U87MG. J Neurochem 1998; 71:1837–1845.PubMedCrossRefGoogle Scholar
  32. 32.
    Hu YS, Zhang QL, Tian ZG et al. [Significance of the unbalanced expression of Th1/Th2 type cytokines in human glioma]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2001; 23:594–598.PubMedGoogle Scholar
  33. 33.
    Li G, Hu YS, Li XG et al. Expression and switching of TH1/TH2 type cytokines gene in human gliomas. Chin Med Sci J 2005; 20:268–272.PubMedGoogle Scholar
  34. 34.
    Roussel E, Gingras MC, Grimm EA et al. Predominance of a type 2 intratumoural immune response in fresh tumour-infiltrating lymphocytes from human gliomas. Clin Exp Immunol 1996; 105:344–352.PubMedCrossRefGoogle Scholar
  35. 35.
    Huettner C, Czub S, Kerkau S et al. Interleukin 10 is expressed in human gliomas in vivo and increases glioma cell proliferation and motility in vitro. Anticancer Res 1997; 17:3217–3224.PubMedGoogle Scholar
  36. 36.
    Hishii M, Nitta T, Ishida H et al. Human glioma-derived interleukin-10 inhibits antitumor immune responses in vitro. Neurosurgery 1995; 37:1160–1166; discussion 1166–1167.PubMedCrossRefGoogle Scholar
  37. 37.
    Wagner S, Czub S, Greif M et al. Microglial/macrophage expression of interleukin 10 in human glioblastomas. Int J Cancer 1999; 82:12–16.PubMedCrossRefGoogle Scholar
  38. 38.
    Samaras V, Piperi C, Korkolopoulou P et al. Application of the ELISPOT method for comparative analysis of interleukin (IL)-6 and IL-10 secretion in peripheral blood of patients with astroglial tumors. Mol Cell Biochem 2007; 304:343–351.PubMedCrossRefGoogle Scholar
  39. 39.
    Murphy-Ullrich JE. The de-adhesive activity of matricellular proteins: is intermediate cell adhesion an adaptive state? J Clin Invest 2001; 107:785–790.PubMedCrossRefGoogle Scholar
  40. 40.
    Sage EH. Regulation of interactions between cells and extracellular matrix: a command performance on several stages. J Clin Invest 2001; 107:781–783.PubMedCrossRefGoogle Scholar
  41. 41.
    Erickson HP. Gene knockouts of c-src, transforming growth factor beta 1 and tenascin suggest superfluous, nonfunctional expression of proteins. J Cell Biol 1993; 120:1079–1081.PubMedCrossRefGoogle Scholar
  42. 42.
    Erickson HP. A tenascin knockout with a phenotype. Nat Genet 1997; 17:5–7.PubMedCrossRefGoogle Scholar
  43. 43.
    Jones PL, Jones FS. Tenascin-C in development and disease: gene regulation and cell function. Matrix Biol 2000; 19:581–596.PubMedCrossRefGoogle Scholar
  44. 44.
    Hemesath TJ, Marton LS, Stefansson K. Inhibition of T-cell activation by the extracellular matrix protein tenascin. J Immunol 1994; 152:5199–5207.PubMedGoogle Scholar
  45. 45.
    Puente Navazo MD, Valmori D, Ruegg C. The alternatively spliced domain TnFnIII A1A2 of the extracellular matrix protein tenascin-C suppresses activation-induced T-lymphocyte proliferation and cytokine production. J Immunol 2001; 167:6431–6440.PubMedGoogle Scholar
  46. 46.
    Parekh K, Ramachandran S, Cooper J et al. Tenascin-C, over expressed in lung cancer down regulates effector functions of tumor infiltrating lymphocytes. Lung Cancer 2005; 47:17–29.PubMedCrossRefGoogle Scholar
  47. 47.
    Bodmer S, Strommer K, Frei K et al. Immunosuppression and transforming growth factor-beta in glioblastoma. Preferential production of transforming growth factor-beta 2. J Immunol 1989; 143:3222–3229.PubMedGoogle Scholar
  48. 48.
    Tada T, Yabu K, Kobayashi S. Detection of active form of transforming growth factor-beta in cerebrospinal fluid of patients with glioma. Jpn J Cancer Res 1993; 84:544–548.PubMedCrossRefGoogle Scholar
  49. 49.
    de Martin R, Haendler B, Hofer-Warbinek R et al. Complementary DNA for human glioblastoma-derived T-cell suppressor factor, a novel member of the transforming growth factor-beta gene family. EMBO J 1987; 6:3673–3677.PubMedGoogle Scholar
  50. 50.
    Wrann M, Bodmer S, de Martin R et al. T-cell suppressor factor from human glioblastoma cells is a 12.5-kd protein closely related to transforming growth factor-beta. EMBO J 1987; 6:1633–1636.PubMedGoogle Scholar
  51. 51.
    Eberhart CE, Coffey RJ, Radhika A et al. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 1994; 107:1183–1188.PubMedGoogle Scholar
  52. 52.
    Wolff H, Saukkonen K, Anttila S et al. Expression of cyclooxygenase-2 in human lung carcinoma. Cancer Res 1998; 58:4997–5001.PubMedGoogle Scholar
  53. 53.
    Mohammed SI, Knapp DW, Bostwick DG et al. Expression of cyclooxygenase-2 (COX-2) in human invasive transitional cell carcinoma (TCC) of the urinary bladder. Cancer Res 1999; 59:5647–5650.PubMedGoogle Scholar
  54. 54.
    Shono T, Tofilon PJ, Bruner JM et al. Cyclooxygenase-2 expression in human gliomas: prognostic significance and molecular correlations. Cancer Res 2001; 61:4375–4381.PubMedGoogle Scholar
  55. 55.
    Joki T, Heese O, Nikas DC et al. Expression of cyclooxygenase 2 (COX-2) in human glioma and in vitro inhibition by a specific COX-2 inhibitor, NS-398. Cancer Res 2000; 60:4926–4931.PubMedGoogle Scholar
  56. 56.
    Phipps RP, Stein SH, Roper RL. A new view of prostaglandin E regulation of the immune response. Immunol Today 1991; 12:349–352.PubMedCrossRefGoogle Scholar
  57. 57.
    Roper RL, Phipps RP. Prostaglandin E2 regulation of the immune response. Adv Prostaglandin Thromboxane Leukot Res 1994; 22:101–111.PubMedGoogle Scholar
  58. 58.
    Kunkel SL, Spengler M, May MA et al. Prostaglandin E2 regulates macrophage-derived tumor necrosis factor gene expression. J Biol Chem 1988; 263:5380–5384.PubMedGoogle Scholar
  59. 59.
    van der Pouw Kraan TC, Boeije LC, Smeenk RJ et al. Prostaglandin-E2 is a potent inhibitor of human interleukin 12 production. J Exp Med 1995; 181:775–779.PubMedCrossRefGoogle Scholar
  60. 60.
    Harizi H, Juzan M, Grosset C et al. Dendritic cells issued in vitro from bone marrow produce PGE(2) that contributes to the immunomodulation induced by antigen-presenting cells. Cell Immunol 2001; 209:19–28.PubMedCrossRefGoogle Scholar
  61. 61.
    Williams JA, Shacter E. Regulation of macrophage cytokine production by prostaglandin E2. Distinct roles of cyclooxygenase-1 and-2. J Biol Chem 1997; 272:25693–25699.PubMedCrossRefGoogle Scholar
  62. 62.
    Strassmann G, Patil-Koota V, Finkelman F et al. Evidence for the involvement of interleukin 10 in the differential deactivation of murine peritoneal macrophages by prostaglandin E2. J Exp Med 1994; 180:2365–2370.PubMedCrossRefGoogle Scholar
  63. 63.
    Fiorentino DF, Zlotnik A, Vieira P et al. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol 1991; 146:3444–3451.PubMedGoogle Scholar
  64. 64.
    Harizi H, Juzan M, Pitard V et al. Cyclooxygenase-2-issued prostaglandin e(2) enhances the production of endogenous IL-10, which down-regulates dendritic cell functions. J Immunol 2002; 168:2255–2263.PubMedGoogle Scholar
  65. 65.
    Akasaki Y, Liu G, Chung NH et al. Induction of a CD4+ T regulatory type 1 response by cyclooxygenase-2-overexpressing glioma. J Immunol 2004; 173:4352–4359.PubMedGoogle Scholar
  66. 66.
    Kokoglu E, Tuter Y, Sandikci KS et al. Prostaglandin E2 levels in human brain tumor tissues and arachidonic acid levels in the plasma membrane of human brain tumors. Cancer Lett 1998; 132:17–21.PubMedCrossRefGoogle Scholar
  67. 67.
    Loh JK, Hwang SL, Lieu AS et al. The alteration of prostaglandin E2 levels in patients with brain tumors before and after tumor removal. J Neurooncol 2002; 57:147–150.PubMedCrossRefGoogle Scholar
  68. 68.
    Rozic JG, Chakraborty C, Lala PK. Cyclooxygenase inhibitors retard murine mammary tumor progression by reducing tumor cell migration, invasiveness and angiogenesis. Int J Cancer 2001; 93:497–506.PubMedCrossRefGoogle Scholar
  69. 69.
    Attiga FA, Fernandez PM, Weeraratna AT et al. Inhibitors of prostaglandin synthesis inhibit human prostate tumor cell invasiveness and reduce the release of matrix metalloproteinases. Cancer Res 2000; 60:4629–4637.PubMedGoogle Scholar
  70. 70.
    Kundu N, Fulton AM. Selective cyclooxygenase (COX)-1 or COX-2 inhibitors control metastatic disease in a murine model of breast cancer. Cancer Res 2002; 62:2343–2346.PubMedGoogle Scholar
  71. 71.
    Connolly EM, Harmey JH, O’Grady T et al. Cyclo-oxygenase inhibition reduces tumour growth and metastasis in an orthotopic model of breast cancer. Br J Cancer 2002; 87:231–237.PubMedCrossRefGoogle Scholar
  72. 72.
    Lalier L, Cartron PF, Pedelaborde F et al. Increase in PGE2 biosynthesis induces a Bax dependent apoptosis correlated to patients’ survival in glioblastoma multiforme. Oncogene 2007; 26:4999–5009.PubMedCrossRefGoogle Scholar
  73. 73.
    Chouaib S, Bertoglio JH. Prostaglandins E as modulators of the immune response. Lymphokine Res Fall 1988; 7:237–245.Google Scholar
  74. 74.
    Goodwin JS, Ceuppens J. Regulation of the immune response by prostaglandins. J Clin Immunol 1983; 3:295–315.PubMedCrossRefGoogle Scholar
  75. 75.
    Rappaport RS, Dodge GR. Prostaglandin E inhibits the production of human interleukin 2. J Exp Med 1982; 155:943–948.PubMedCrossRefGoogle Scholar
  76. 76.
    Kuppner MC, Sawamura Y, Hamou MF et al. Influence of PGE2-and cAMP-modulating agents on human glioblastoma cell killing by interleukin-2-activated lymphocytes. J Neurosurg 1990; 72:619–625.PubMedCrossRefGoogle Scholar
  77. 77.
    Lauro GM, Di Lorenzo N, Grossi M et al. Prostaglandin E2 as an immunomodulating factor released in vitro by human glioma cells. Acta Neuropathol 1986; 69:278–282.PubMedCrossRefGoogle Scholar
  78. 78.
    Sawamura Y, Diserens AC, de Tribolet N. In vitro prostaglandin E2 production by glioblastoma cells and its effect on interleukin-2 activation of oncolytic lymphocytes. J Neurooncol 1990; 9:125–130.PubMedCrossRefGoogle Scholar
  79. 79.
    Nakano Y, Kuroda E, Kito T et al. Induction of macrophagic prostaglandin E2 synthesis by glioma cells. J Neurosurg 2006; 104:574–582.PubMedCrossRefGoogle Scholar
  80. 80.
    Nakano Y, Kuroda E, Kito T et al. Induction of prostaglandin E2 synthesis and microsomal prostaglandin E synthase-1 expression in murine microglia by glioma-derived soluble factors. Laboratory investigation. J Neurosurg 2008; 108:311–319.PubMedCrossRefGoogle Scholar
  81. 81.
    Anderson RC, Anderson DE, Elder JB et al. Lack of B7 expression, not human leukocyte antigen expression, facilitates immune evasion by human malignant gliomas. Neurosurgery 2007; 60(6):1129–1136; discussion 1136.PubMedCrossRefGoogle Scholar
  82. 82.
    Bromberg J. Stat proteins and oncogenesis. J Clin Invest 2002; 109(9):1139–1142.PubMedGoogle Scholar
  83. 83.
    Brantley EC, Benveniste EN. Signal transducer and activator of transcription-3: a molecular hub for signaling pathways in gliomas. Mol Cancer Res 2008; 6(5):675–684.PubMedCrossRefGoogle Scholar
  84. 84.
    Chung CD, Liao J, Liu B et al. Specific inhibition of Stat3 signal transduction by PIAS3. Science 1997; 278(5344):1803–1805.PubMedCrossRefGoogle Scholar
  85. 85.
    Pillemer BB, Xu H, Oriss TB et al. Deficient SOCS3 expression in CD4+CD25+FoxP3+ regulatory T-cells and SOCS3-mediated suppression of Treg function. Eur J Immunol 2007; 37(8):2082–2089.PubMedCrossRefGoogle Scholar
  86. 86.
    Yu H, Kortylewski M, Pardoll D. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol 2007; 7(1):41–51.PubMedCrossRefGoogle Scholar
  87. 87.
    Wang T, Niu G, Kortylewski M et al. Regulation of the innate and adaptive immune responses by STAT3 signaling in tumor cells. Nat Med 2004; 10(1):48–54.PubMedCrossRefGoogle Scholar
  88. 88.
    Kortylewski M, Kujawski M, Wang T et al. Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat Med 2005; 11(12):1314–1321.PubMedCrossRefGoogle Scholar
  89. 89.
    Almand B, Resser JR, Lindman B et al. Clinical significance of defective dendritic cell differentiation in cancer. Clin Cancer Res 2000; 6(5):1755–1766.PubMedGoogle Scholar
  90. 90.
    Kasprzycka M, Marzec M, Liu X et al. Nucleophosmin/anaplastic lymphoma kinase (NPM/ALK) oncoprotein induces the T regulatory cell phenotype by activating STAT3. Proc Natl Acad Sci USA 2006; 103(26):9964–9969.PubMedCrossRefGoogle Scholar
  91. 91.
    Jordan JT, Sun W, Hussain SF et al. Preferential migration of regulatory T-cells mediated by glioma-secreted chemokines can be blocked with chemotherapy. Cancer Immunol Immunother 2008; 57(1):123–131.PubMedCrossRefGoogle Scholar
  92. 92.
    Abou-Ghazal M, Yang DS, Qiao W et al. The incidence, correlation with tumor-infiltrating inflammation and prognosis of phosphorylated STAT3 expression in human gliomas. Clin Cancer Res 2008; 14(24):8228–8235.PubMedCrossRefGoogle Scholar
  93. 93.
    Hussain SF, Kong LY, Jordan J et al. A novel small molecule inhibitor of signal transducers and activators of transcription 3 reverses immune tolerance in malignant glioma patients. Cancer Res 2007; 67(20):9630–9636.PubMedCrossRefGoogle Scholar
  94. 94.
    Ichikawa M, Chen L. Role of B7-H1 and B7-H4 molecules in down-regulating effector phase of T-cell immunity: novel cancer escaping mechanisms. Front Biosci 2005; 10:2856–2860.PubMedCrossRefGoogle Scholar
  95. 95.
    Ghebeh H, Mohammed S, Al-Omair A et al. The B7-H1 (PD-L1) T-lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factors. Neoplasia 2006; 8(3):190–198.PubMedCrossRefGoogle Scholar
  96. 96.
    Tsushima F, Tanaka K, Otsuki N et al. Predominant expression of B7-H1 and its immunoregulatory roles in oral squamous cell carcinoma. Oral Oncol 2006; 42(3):268–274.PubMedCrossRefGoogle Scholar
  97. 97.
    Strome SE, Dong H, Tamura H et al. B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma. Cancer Res 2003; 63(19):6501–6505.PubMedGoogle Scholar
  98. 98.
    Wintterle S, Schreiner B, Mitsdoerffer M et al. Expression of the B7-related molecule B7-H1 by glioma cells: a potential mechanism of immune paralysis. Cancer Res 2003; 63(21):7462–7467.PubMedGoogle Scholar
  99. 99.
    Dong H, Chen L. B7-H1 pathway and its role in the evasion of tumor immunity. J Mol Med 2003; 81(5):281–287.PubMedGoogle Scholar
  100. 100.
    Tamura H, Dong H, Zhu G et al. B7-H1 costimulation preferentially enhances CD28-independent T-helper cell function. Blood 2001; 97(6):1809–1816.PubMedCrossRefGoogle Scholar
  101. 101.
    Dong H, Strome SE, Salomao DR et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 2002; 8(8):793–800.PubMedGoogle Scholar
  102. 102.
    Hirano F, Kaneko K, Tamura H et al. Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res 2005; 65(3):1089–1096.PubMedGoogle Scholar
  103. 103.
    Blank C, Brown I, Peterson AC et al. PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T-cell receptor (TCR) transgenic CD8+ T-cells. Cancer Res 2004; 64(3):1140–1145.PubMedCrossRefGoogle Scholar
  104. 104.
    Blank C, Kuball J, Voelkl S et al. Blockade of PD-L1 (B7-H1) augments human tumor-specific T-cell responses in vitro. Int J Cancer 2006; 119(2):317–327.PubMedCrossRefGoogle Scholar
  105. 105.
    Iwai Y, Ishida M, Tanaka Y et al. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA 2002; 99(19):12293–12297.PubMedCrossRefGoogle Scholar
  106. 106.
    Blank C, Gajewski TF, Mackensen A. Interaction of PD-L1 on tumor cells with PD-1 on tumor-specific T-cells as a mechanism of immune evasion: implications for tumor immunotherapy. Cancer Immunol Immunother 2005; 54(4):307–314.PubMedCrossRefGoogle Scholar
  107. 107.
    Karre K, Ljunggren HG, Piontek G, Kiessling R. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature 1986; 319(6055):675–678.PubMedCrossRefGoogle Scholar
  108. 108.
    Diefenbach A, Jensen ER, Jamieson AM et al. Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity. Nature 2001; 413(6852):165–171.PubMedCrossRefGoogle Scholar
  109. 109.
    Cerwenka A, Baron JL, Lanier LL. Ectopic expression of retinoic acid early inducible-1 gene (RAE-1) permits natural killer cell-mediated rejection of a MHC class I-bearing tumor in vivo. Proc Natl Acad Sci USA 2001; 98(20):11521–11526.PubMedCrossRefGoogle Scholar
  110. 110.
    Dix AR, Brooks WH, Roszman TL et al. Immune defects observed in patients with primary malignant brain tumors. J Neuroimmunol 1999; 100(1–2):216–232.CrossRefGoogle Scholar
  111. 111.
    Braun DP, Penn RD, Harris JE. Regulation of natural killer cell function by glass-adherent cells in patients with primary intracranial malignancies. Neurosurgery 1984; 15(1):29–33.PubMedCrossRefGoogle Scholar
  112. 112.
    Proescholdt MA, Merrill MJ, Ikejiri B et al. Site-specific immune response to implanted gliomas. J Neurosurg 2001; 95(6):1012–1019.PubMedCrossRefGoogle Scholar
  113. 113.
    Aldemir H, Prod’homme V, Dumaurier MJ et al. Cutting edge: lectin-like transcript 1 is a ligand for the CD161 receptor. J Immunol 2005; 175(12):7791–7795.PubMedGoogle Scholar
  114. 114.
    Roth P, Mittelbronn M, Wick W et al. Malignant glioma cells counteract antitumor immune responses through expression of lectin-like transcript-1. Cancer Res 2007; 676(8):3540–3544.CrossRefGoogle Scholar
  115. 115.
    Boomer JS, Derks RA, Lee GW et al. Regeneration and tolerance factor is expressed during T-lymphocyte activation and plays a role in apoptosis. Hum Immunol 2001; 62(6):577–588.PubMedCrossRefGoogle Scholar
  116. 116.
    Roth P, Aulwurm S, Gekel I et al. Regeneration and tolerance factor: a novel mediator of glioblastoma-associated immunosuppression. Cancer Res 2006; 66(7):3852–3858.PubMedCrossRefGoogle Scholar
  117. 117.
    Tachibana O, Nakazawa H, Lampe J et al. Expression of Fas/APO-1 during the progression of astrocytomas. Cancer Res 1995; 55(23):5528–5530.PubMedGoogle Scholar
  118. 118.
    Gratas C, Tohma Y, Van Meir EG et al. Fas ligand expression in glioblastoma cell lines and primary astrocytic brain tumors. Brain Pathol 1997; 7(3):863–869.PubMedCrossRefGoogle Scholar
  119. 119.
    Saas P, Walker PR, Hahne M et al. Fas ligand expression by astrocytoma in vivo: maintaining immune privilege in the brain? J Clin Invest 1997; 99(6):1173–1178.PubMedCrossRefGoogle Scholar
  120. 120.
    Didenko VV, Ngo HN, Minchew C et al. Apoptosis of T-lymphocytes invading glioblastomas multiforme: a possible tumor defense mechanism. J Neurosurg 2002; 96(3):580–584.PubMedCrossRefGoogle Scholar
  121. 121.
    Roth W, Isenmann S, Nakamura M et al. Soluble decoy receptor 3 is expressed by malignant gliomas and suppresses CD95 ligand-induced apoptosis and chemotaxis. Cancer Res 2001; 61(6):2759–2765.PubMedGoogle Scholar
  122. 122.
    Hintzen RQ, Lens SM, Koopman G et al. CD70 represents the human ligand for CD27. Int Immunol 1994; 6(3):477–480.PubMedCrossRefGoogle Scholar
  123. 123.
    Sugita K, Hirose T, Rothstein DM et al. CD27, a member of the nerve growth factor receptor family, is preferentially expressed on CD45RA+ CD4 T-cell clones and involved in distinct immunoregulatory functions. J Immunol 1992; 149(10):3208–3216.PubMedGoogle Scholar
  124. 124.
    Hendriks J, Gravestein LA, Tesselaar K et al. CD27 is required for generation and long-term maintenance of T-cell immunity. Nat Immunol 2000; 1(5):433–440.PubMedCrossRefGoogle Scholar
  125. 125.
    La Rosa FG, Adams FS, Krause GE et al. Inhibition of proliferation and expression of T-antigen in SV40 large T-antigen gene-induced immortalized cells following transplantations. Cancer Lett 1997; 113(1–2):55–60.PubMedCrossRefGoogle Scholar
  126. 126.
    Tesselaar K, Arens R, van Schijndel GM et al. Lethal T-cell immunodeficiency induced by chronic costimulation via CD27-CD70 interactions. Nat Immunol 2003; 4(1):49–54.PubMedCrossRefGoogle Scholar
  127. 127.
    Koenen HJ, Fasse E, Joosten I. CD27/CFSE-based ex vivo selection of highly suppressive alloantigen-specific human regulatory T-cells. J Immunol 2005; 174(12):7573–7583.PubMedGoogle Scholar
  128. 128.
    Chahlavi A, Rayman P, Richmond AL et al. Glioblastomas induce T-lymphocyte death by two distinct pathways involving gangliosides and CD70. Cancer Res 2005; 65(12):5428–5438.PubMedCrossRefGoogle Scholar
  129. 129.
    Kudo D, Rayman P, Horton C et al. Gangliosides expressed by the renal cell carcinoma cell line SK-RC-45 are involved in tumor-induced apoptosis of T-cells. Cancer Res 2003; 636(7):1676–1683.Google Scholar
  130. 130.
    Ledeen RW, Wu G. Nuclear lipids: key signaling effectors in the nervous system and other tissues. J Lipid Res 2004; 45(1):1–8.PubMedCrossRefGoogle Scholar
  131. 131.
    Hedberg KM, Mahesparan R, Read TA et al. The glioma-associated gangliosides 3′-isoLM1, GD3 and GM2 show selective area expression in human glioblastoma xenografts in nude rat brains. Neuropathol Appl Neurobiol 2001; 27(6):451–464.PubMedCrossRefGoogle Scholar
  132. 132.
    Markowska-Woyciechowska A, Bronowicz A, Ugorski M et al. Study on ganglioside composition in brain tumours supra-and infratentorial. Neurol Neurochir Pol 2000; 34(6 Suppl):124–130.PubMedGoogle Scholar
  133. 133.
    Mennel HD, Bosslet K, Geissel H et al. Immunohistochemically visualized localisation of gangliosides Glac2 (GD3) and Gtri2 (GD2) in cells of human intracranial tumors. Exp Toxicol Pathol 2000; 52(4):277–285.PubMedCrossRefGoogle Scholar
  134. 134.
    Wagener R, Rohn G, Schillinger G et al. Ganglioside profiles in human gliomas: quantification by microbore high performance liquid chromatography and correlation to histomorphology and grading. Acta Neurochir (Wien) 1999; 141(12):1339–1345.CrossRefGoogle Scholar
  135. 135.
    Ward SG, Westwick J. Chemokines: understanding their role in T-lymphocyte biology. Biochem J 1998; 333(Pt3):457–470.PubMedGoogle Scholar
  136. 136.
    Mantovani A. Chemokines. Introduction and overview. Chem Immunol 1999; 72:1–6.PubMedCrossRefGoogle Scholar
  137. 137.
    Mantovani A, Allavena P, Sozzani S et al. Chemokines in the recruitment and shaping of the leukocyte infiltrate of tumors. Semin Cancer Biol 2004; 14:155–160.PubMedCrossRefGoogle Scholar
  138. 138.
    Rollins BJ. Chemokines. Blood 1997; 90:909–928.Google Scholar
  139. 139.
    Gerard C, Rollins BJ. Chemokines and disease. Nat Immunol 2001; 2:108–115.PubMedCrossRefGoogle Scholar
  140. 140.
    Rollins BJ. Inflammatory chemokines in cancer growth and progression. Eur J Cancer 2006; 42:760–767.PubMedCrossRefGoogle Scholar
  141. 141.
    Zhou Y, Larsen PH, Hao C et al. CXCR4 is a major chemokine receptor on glioma cells and mediates their survival. J Biol Chem 2002; 277:49481–49487.PubMedCrossRefGoogle Scholar
  142. 142.
    Li M, Ransohoff RM. Multiple roles of chemokine CXCL12 in the central nervous system: a migration from immunology to neurobiology. Prog Neurobiol 2008; 84:116–131.PubMedCrossRefGoogle Scholar
  143. 143.
    Choi C, Xu X, Oh JW et al. Fas-induced expression of chemokines in human glioma cells: involvement of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase. Cancer Res 2001; 61:3084–3091.PubMedGoogle Scholar
  144. 144.
    Curiel TJ, Coukos G, Zou L et al. Specific recruitment of regulatory T-cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 2004; 10:942–949.PubMedCrossRefGoogle Scholar
  145. 145.
    Mazzoni A, Bronte V, Visintin A et al. Myeloid suppressor lines inhibit T-cell responses by an NO-dependent mechanism. J Immunol 2002; 168:689–695.PubMedGoogle Scholar
  146. 146.
    Duwe AK, Singhal SK. The immunoregulatory role of bone marrow. II. Characterization of a suppressor cell inhibiting the in vitro antibody response. Cell Immunol 1979; 43:372–381.PubMedCrossRefGoogle Scholar
  147. 147.
    Duwe AK, Singhal SK. The immunoregulatory role of bone marrow. I. Suppression of the induction of antibody responses to T-dependent and T-independent antigens by cells in the bone marrow. Cell Immunol 1979; 43:362–371.PubMedCrossRefGoogle Scholar
  148. 148.
    Young MR, Newby M, Wepsic HT. Hematopoiesis and suppressor bone marrow cells in mice bearing large metastatic Lewis lung carcinoma tumors. Cancer Res 1987; 47:100–105.PubMedGoogle Scholar
  149. 149.
    Bronte V, Kasic T, Gri G et al. Boosting antitumor responses of T-lymphocytes infiltrating human prostate cancers. J Exp Med 2005; 201:1257–1268.PubMedCrossRefGoogle Scholar
  150. 150.
    Kusmartsev S, Cheng F, Yu B et al. All-trans-retinoic acid eliminates immature myeloid cells from tumor-bearing mice and improves the effect of vaccination. Cancer Res 2003; 63:4441–4449.PubMedGoogle Scholar
  151. 151.
    Kusmartsev S, Gabrilovich DI. Inhibition of myeloid cell differentiation in cancer: the role of reactive oxygen species. J Leukoc Biol 2003; 74:186–196.PubMedCrossRefGoogle Scholar
  152. 152.
    Bronte V, Apolloni E, Cabrelle A et al. Identification of a CD11b(+)/Gr-1(+)/CD31(+) myeloid progenitor capable of activating or suppressing CD8(+) T-cells. Blood 2000; 96:3838–3846.PubMedGoogle Scholar
  153. 153.
    Gabrilovich DI, Bronte V, Chen SH et al. The terminology issue for myeloid-derived suppressor cells. Cancer Res 2007; 67:425; author reply 426.PubMedCrossRefGoogle Scholar
  154. 154.
    Pak AS, Wright MA, Matthews JP et al. 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 1995; 1:95–103.PubMedGoogle Scholar
  155. 155.
    Lin EY, Gouon-Evans V, Nguyen AV et al. The macrophage growth factor CSF-1 in mammary gland development and tumor progression. J Mammary Gland Biol Neoplasia 2002; 7:147–162.PubMedCrossRefGoogle Scholar
  156. 156.
    Menetrier-Caux C, Montmain G, Dieu MC et al. Inhibition of the differentiation of dendritic cells from CD34(+) progenitors by tumor cells: role of interleukin-6 and macrophage colony-stimulating factor. Blood 1998; 92:4778–4791.PubMedGoogle Scholar
  157. 157.
    Grauer OM, Nierkens S, Bennink E et al. CD4+FoxP3+ regulatory T-cells gradually accumulate in gliomas during tumor growth and efficiently suppress antiglioma immune responses in vivo. Int J Cancer 2007; 121:95–105.PubMedCrossRefGoogle Scholar
  158. 158.
    Yong Z, Chang L, Mei YX et al. Role and mechanisms of CD4+CD25+ regulatory T-cells in the induction and maintenance of transplantation tolerance. Transpl Immunol 2007; 17:120–129.PubMedCrossRefGoogle Scholar
  159. 159.
    Brusko TM, Putnam AL, Bluestone JA. Human regulatory T-cells: role in autoimmune disease and therapeutic opportunities. Immunol Rev 2008; 223:371–390.PubMedCrossRefGoogle Scholar
  160. 160.
    Ling KL, Pratap SE, Bates GJ et al. Increased frequency of regulatory T-cells in peripheral blood and tumour infiltrating lymphocytes in colorectal cancer patients. Cancer Immun 2007; 7:7.PubMedGoogle Scholar
  161. 161.
    Ichihara F, Kono K, Takahashi A et al. Increased populations of regulatory T-cells in peripheral blood and tumor-infiltrating lymphocytes in patients with gastric and esophageal cancers. Clin Cancer Res 2003; 9:4404–4408.PubMedGoogle Scholar
  162. 162.
    Liyanage UK, Moore TT, Joo HG et al. Prevalence of regulatory T-cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol 2002; 169:2756–2761.PubMedGoogle Scholar
  163. 163.
    Okita R, Saeki T, Takashima S et al. CD4+CD25+ regulatory T-cells in the peripheral blood of patients with breast cancer and nonsmall cell lung cancer. Oncol Rep 2005; 14: 1269–1273.PubMedGoogle Scholar
  164. 164.
    Sakaguchi S, Sakaguchi N, Asano M et al. Immunologic self-tolerance maintained by activated T-cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 1995; 155:1151–1164.PubMedGoogle Scholar
  165. 165.
    Toda A, Piccirillo CA. Development and function of naturally occurring CD4+CD25+ regulatory T-cells. J Leukoc Biol 2006; 80:458–470.PubMedCrossRefGoogle Scholar
  166. 166.
    Itoh M, Takahashi T, Sakaguchi N et al. Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T-cells as a key function of the thymus in maintaining immunologic self-tolerance. J Immunol 1999; 162:5317–5326.PubMedGoogle Scholar
  167. 167.
    Schimpl A, Berberich I, Kneitz B et al. IL-2 and autoimmune disease. Cytokine Growth Factor Rev 2002; 13:369–378.PubMedCrossRefGoogle Scholar
  168. 168.
    Bayer AL, Yu A, Adeegbe D et al. Essential role for interleukin-2 for CD4(+)CD25(+) T regulatory cell development during the neonatal period. J Exp Med 2005; 201:769–777.PubMedCrossRefGoogle Scholar
  169. 169.
    Bayer AL, Yu A, Malek TR. Function of the IL-2R for thymic and peripheral CD4+CD25+ Foxp3+ T regulatory cells. J Immunol 2007; 178:4062–4071.PubMedGoogle Scholar
  170. 170.
    Malek TR, Yu A, Vincek V et al. CD4 regulatory T-cells prevent lethal autoimmunity in IL-2Rbeta-deficient mice. Implications for the nonredundant function of IL-2. Immunity 2002; 17:167–178.PubMedCrossRefGoogle Scholar
  171. 171.
    Malek TR. The main function of IL-2 is to promote the development of T regulatory cells. J Leukoc Biol 2003; 74:961–965.PubMedCrossRefGoogle Scholar
  172. 172.
    de la Rosa M, Rutz S, Dorninger H et al. Interleukin-2 is essential for CD4+CD25+ regulatory T-cell function. Eur J Immunol 2004; 34:2480–2488.PubMedCrossRefGoogle Scholar
  173. 173.
    Moriggl R, Topham DJ, Teglund S et al. Stat5 is required for IL-2-induced cell cycle progression of peripheral T-cells. Immunity 1999; 10:249–259.PubMedCrossRefGoogle Scholar
  174. 174.
    Van Parijs L, Refaeli Y, Lord JD et al. Uncoupling IL-2 signals that regulate T-cell proliferation, survival and Fas-mediated activation-induced cell death. Immunity 1999; 11:281–288.PubMedCrossRefGoogle Scholar
  175. 175.
    Antov A, Yang L, Vig M et al. Essential role for STAT5 signaling in CD25+CD4+ regulatory T-cell homeostasis and the maintenance of self-tolerance. J Immunol 2003; 171:3435–3441.PubMedGoogle Scholar
  176. 176.
    Snow JW, Abraham N, Ma MC et al. Loss of tolerance and autoimmunity affecting multiple organs in STAT5A/5B-deficient mice. J Immunol 2003; 171:5042–5050.PubMedGoogle Scholar
  177. 177.
    Burchill MA, Goetz CA, Prlic M et al. Distinct effects of STAT5 activation on CD4+ and CD8+ T-cell homeostasis: development of CD4+CD25+ regulatory T-cells versus CD8+ memory T-cells. J Immunol 2003; 171:5853–5864.PubMedGoogle Scholar
  178. 178.
    Hori S, Nomura T, Sakaguchi S. Control of regulatory T-cell development by the transcription factor Foxp3. Science 2003; 299:1057–1061.PubMedCrossRefGoogle Scholar
  179. 179.
    Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T-cells. Nat Immunol 2003; 4:330–336.PubMedCrossRefGoogle Scholar
  180. 180.
    Yagi H, Nomura T, Nakamura K et al. Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T-cells. Int Immunol 2004; 16(:1643–1656.PubMedCrossRefGoogle Scholar
  181. 181.
    Qiao M, Thornton AM, Shevach EM. CD4+ CD25+ [corrected] regulatory T-cells render naive CD4+ CD25-T-cells anergic and suppressive. Immunology 2007; 120:447–455.PubMedCrossRefGoogle Scholar
  182. 182.
    Sundstedt A, O’Neill EJ, Nicolson KS et al. Role for IL-10 in suppression mediated by peptide-induced regulatory T-cells in vivo. J Immunol 2003; 170:1240–1248.PubMedGoogle Scholar
  183. 183.
    Vieira PL, Christensen JR, Minaee S et al. IL-10-secreting regulatory T-cells do not express Foxp3 but have comparable regulatory function to naturally occurring CD4+CD25+ regulatory T-cells. J Immunol 2004; 172:5986–5993.PubMedGoogle Scholar
  184. 184.
    Miller A, Lider O, Roberts AB et al. Suppressor T-cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor beta after antigen-specific triggering. Proc Natl Acad Sci USA 1992; 89:421–425.PubMedCrossRefGoogle Scholar
  185. 185.
    Zhang X, Izikson L, Liu L et al. Activation of CD25(+)CD4(+) regulatory T-cells by oral antigen administration. J Immunol 2001; 167:4245–4253.PubMedGoogle Scholar
  186. 186.
    Levings MK, Gregori S, Tresoldi E et al. Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells. Blood 2005; 105:1162–1169.PubMedCrossRefGoogle Scholar
  187. 187.
    Takahashi Y, Onda M, Tanaka N et al. Establishment and characterization of two new rectal neuroendocrine cell carcinoma cell lines. Digestion 2000; 62:262–270.PubMedCrossRefGoogle Scholar
  188. 188.
    Manzotti CN, Tipping H, Perry LC et al. Inhibition of human T-cell proliferation by CTLA-4 utilizes CD80 and requires CD25+ regulatory T-cells. Eur J Immunol 2002; 32:2888–2896.PubMedCrossRefGoogle Scholar
  189. 189.
    Tang Q, Boden EK, Henriksen KJ et al. Distinct roles of CTLA-4 and TGF-beta in CD4+CD25+ regulatory T-cell function. Eur J Immunol 2004; 34:2996–3005.PubMedCrossRefGoogle Scholar
  190. 190.
    Pae HO, Oh GS, Choi BM et al. Differential expressions of heme oxygenase-1 gene in CD25-and CD25+ subsets of human CD4+ T-cells. Biochem Biophys Res Commun 2003; 306:701–705.PubMedCrossRefGoogle Scholar
  191. 191.
    Choi BM, Pae HO, Jeong YR et al. Critical role of heme oxygenase-1 in Foxp3-mediated immune suppression. Biochem Biophys Res Commun 2005; 327:1066–1071.PubMedCrossRefGoogle Scholar
  192. 192.
    Pae HO, Oh GS, Choi BM et al. Carbon monoxide produced by heme oxygenase-1 suppresses T-cell proliferation via inhibition of IL-2 production. J Immunol 2004; 172:4744–4751.PubMedGoogle Scholar
  193. 193.
    Song R, Zhou Z, Kim PK et al. Carbon monoxide promotes Fas/CD95-induced apoptosis in Jurkat cells. J Biol Chem 2004; 279:44327–44334.PubMedCrossRefGoogle Scholar
  194. 194.
    Curtin JF, Candolfi M, Fakhouri TM et al. Treg depletion inhibits efficacy of cancer immunotherapy: implications for clinical trials. PLoS ONE 2008; 3:e1983.CrossRefGoogle Scholar
  195. 195.
    Maines MD, Polevoda B, Coban T et al. Neuronal overexpression of heme oxygenase-1 correlates with an attenuated exploratory behavior and causes an increase in neuronal NADPH diaphorase staining. J Neurochem 1998; 70:2057–2069.PubMedCrossRefGoogle Scholar
  196. 196.
    Stocker R, Glazer AN, Ames BN. Antioxidant activity of albumin-bound bilirubin. Proc Natl Acad Sci USA 1987; 84:5918–5922.PubMedCrossRefGoogle Scholar
  197. 197.
    Stocker R, Yamamoto Y, McDonagh AF et al. Bilirubin is an antioxidant of possible physiological importance. Science 1987; 235:1043–1046.PubMedCrossRefGoogle Scholar
  198. 198.
    Ewing JF, Haber SN, Maines MD. Normal and heat-induced patterns of expression of heme oxygenase-1 (HSP32) in rat brain: hyperthermia causes rapid induction of mRNA and protein. J Neurochem 1992; 58:1140–1149.PubMedCrossRefGoogle Scholar
  199. 199.
    Panahian N, Yoshiura M, Maines MD. Overexpression of heme oxygenase-1 is neuroprotective in a model of permanent middle cerebral artery occlusion in transgenic mice. J Neurochem 1999; 72:1187–1203.PubMedCrossRefGoogle Scholar
  200. 200.
    Fukuda K, Panter SS, Sharp FR et al. Induction of heme oxygenase-1 (HO-1) after traumatic brain injury in the rat. Neurosci Lett 1995; 199:127–130.PubMedCrossRefGoogle Scholar
  201. 201.
    Nimura T, Weinstein PR, Massa SM et al. Heme oxygenase-1 (HO-1) protein induction in rat brain following focal ischemia. Brain Res Mol Brain Res 1996; 37:201–208.PubMedCrossRefGoogle Scholar
  202. 202.
    Schipper HM, Cisse S, Stopa EG. Expression of heme oxygenase-1 in the senescent and Alzheimer-diseased brain. Ann Neurol 1995; 37:758–768.PubMedCrossRefGoogle Scholar
  203. 203.
    Hara E, Takahashi K, Tominaga T et al. Expression of heme oxygenase and inducible nitric oxide synthase mRNA in human brain tumors. Biochem Biophys Res Commun 1996; 224:153–158.PubMedCrossRefGoogle Scholar
  204. 204.
    Nishie A, Ono M, Shono T et al. Macrophage infiltration and heme oxygenase-1 expression correlate with angiogenesis in human gliomas. Clin Cancer Res 1999; 5:1107–1113.PubMedGoogle Scholar
  205. 205.
    Deininger MH, Meyermann R, Trautmann K et al. Heme oxygenase (HO)-1 expressing macrophages/microglial cells accumulate during oligodendroglioma progression. Brain Res 2000; 882:1–8.PubMedCrossRefGoogle Scholar
  206. 206.
    Choi BM, Pae HO, Jeong YR et al. Overexpression of heme oxygenase (HO)-1 renders Jurkat T-cells resistant to fas-mediated apoptosis: involvement of iron released by HO-1. Free Radic Biol Med 2004; 36:858–871.PubMedCrossRefGoogle Scholar
  207. 207.
    El Andaloussi A, Lesniak MS. CD4+ CD25+ FoxP3+ T-cell infiltration and heme oxygenase-1 expression correlate with tumor grade in human gliomas. J Neurooncol 2007; 83:145–152.PubMedCrossRefGoogle Scholar
  208. 208.
    Schlingensiepen KH, Schlingensiepen R, Steinbrecher A et al. Targeted tumor therapy with the TGF-beta 2 antisense compound AP 12009. Cytokine Growth Factor Rev 2006; 17:129–139.PubMedCrossRefGoogle Scholar
  209. 209.
    Iwamaru A, Szymanski S, Iwado E et al. A novel inhibitor of the STAT3 pathway induces apoptosis in malignant glioma cells both in vitro and in vivo. Oncogene 2007; 26:2435–2444.PubMedCrossRefGoogle Scholar
  210. 210.
    Foss FM. DAB(389)IL-2 (denileukin diftitox, ONTAK): a new fusion protein technology. Clin Lymphoma 2000; (1 Suppl 1):S27–31.CrossRefGoogle Scholar
  211. 211.
    Barnett B, Kryczek I, Cheng P et al. Regulatory T-cells in ovarian cancer: biology and therapeutic potential. Am J Reprod Immunol 2005; 54:369–377.PubMedCrossRefGoogle Scholar
  212. 212.
    Grauer OM, Sutmuller RP, van Maren W et al. Elimination of regulatory T-cells is essential for an effective vaccination with tumor lysate-pulsed dendritic cells in a murine glioma model. Int J Cancer 2008; 122:1794–1802.PubMedCrossRefGoogle Scholar
  213. 213.
    Heimberger AB, Crotty LE, Archer GE et al. Epidermal growth factor receptor VIII peptide vaccination is efficacious against established intracerebral tumors. Clin Cancer Res 2003; 9:4247–4254.PubMedGoogle Scholar
  214. 214.
    Sampson JH, Archer GE, Mitchell DA et al. Tumor-specific immunotherapy targeting the EGFRvIII mutation in patients with malignant glioma. Semin Immunol 2008; 20:267–275.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2012

Authors and Affiliations

  • Cleo E. Rolle
    • 1
  • Sadhak Sengupta
    • 1
  • Maciej S. Lesniak
    • 2
  1. 1.Department of Surgery, Section of NeurosurgeryThe University of Chicago Pritzker School of MedicineChicagoUSA
  2. 2.Section of NeurosurgeryThe University of ChicagoChicagoUSA

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