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Immunopathology and Immunotherapy of Central Nervous System Cancer

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Cancer Immunology

Abstract

Cancers of the central nervous system (CNS) are unique both in the immunopathology underlying their development and in the challenges they present to designing effective immune-based therapeutic strategies. The immune response in the CNS has fundamental differences from that seen elsewhere in the organism. Moreover, a series of evasion mechanisms have been described for CNS tumors, which limit effective recognition and effective antitumoral cytotoxic responses by the immune system. A series of therapeutic approaches are currently being developed for enhancing and focusing the immune system to elicit and enhance a therapeutic antitumoral response. In this chapter, an overview of the intricacies of the immune system in the CNS within the context of tumor immunology is presented. In addition, some of the most salient immunotherapeutic advances for treatment of CNS tumors are explored.

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References

  1. Davis FG, Freels S, Grutsch J, Barlas S, Brem S. Survival rates in patients with primary malignant brain tumors stratified by patient age and tumor histological type: an analysis based on Surveillance, Epidemiology, and End Results (SEER) data, 1973–1991. J Neurosurg. 1998;88:1–10.

    Article  CAS  PubMed  Google Scholar 

  2. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10:459–66.

    Article  CAS  PubMed  Google Scholar 

  3. Parney I. Basic concepts in glioma immunology. Adv Exp Med Biol. 2012;746:42–52.

    Article  CAS  PubMed  Google Scholar 

  4. Harling-Berg C, Hallett J, Park J, Knopf P. Hierarchy of immune responses to antigen in the normal brain. In: Protective and pathological immune responses in the CNS. Berlin/New York: Springer; 2002. p. 1–22.

    Chapter  Google Scholar 

  5. Gehrmann J, Banati R, Wiessnert C, Hossmann KA, Kreutzberg G. Reactive microglia in cerebral ischaemia: an early mediator of tissue damage? Neuropathol Appl Neurobiol. 1995;21:277–89.

    Article  CAS  PubMed  Google Scholar 

  6. Flavell K, Murray P. Hodgkin’s disease and the Epstein-Barr virus. Mol Pathol. 2000;53:262–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189:12–9.

    Article  CAS  PubMed  Google Scholar 

  8. Cobbs CS, Harkins L, Samanta M, Gillespie GY, Bharara S, King PH, et al. Human cytomegalovirus infection and expression in human malignant glioma. Cancer Res. 2002;62:3347–50.

    CAS  PubMed  Google Scholar 

  9. Fabry Z, Raine CS, Hart MN. Nervous tissue as an immune compartment: the dialect of the immune response in the CNS. Immunol Tod. 1994;15:218–24.

    Article  CAS  Google Scholar 

  10. Beschorner R, Nguyen TD, Gözalan F, Pedal I, Mattern R, Schluesener HJ, et al. CD14 expression by activated parenchymal microglia/macrophages and infiltrating monocytes following human traumatic brain injury. Acta Neuropathol. 2002;103:541–9.

    Article  CAS  PubMed  Google Scholar 

  11. Owens T, Renno T, Taupin V, Krakowski M. Inflammatory cytokines in the brain: does the CNS shape immune responses? Immunol Tod. 1994;15:566–71.

    Article  CAS  Google Scholar 

  12. Ling EA, Wong WC. The origin and nature of ramified and amoeboid microglia: a historical review and current concepts. Glia. 1993;7:9–18.

    Article  CAS  PubMed  Google Scholar 

  13. Goldmann J, Kwidzinski E, Brandt C, Mahlo J, Richter D, Bechmann I. T cells traffic from brain to cervical lymph nodes via the cribroid plate and the nasal mucosa. J Leukoc Biol. 2006;80:797–801.

    Article  CAS  PubMed  Google Scholar 

  14. Cserr HF, Knopf PM. Cervical lymphatics, the blood-brain barrier and the immunoreactivity of the brain: a new view. Immunol Tod. 1992;13:507–12.

    Article  CAS  Google Scholar 

  15. Weller RO, Engelhardt B, Phillips MJ. Lymphocyte targeting of the central nervous system: a review of afferent and efferent CNS‐immune pathways. Brain Pathol. 1996;6:275–88.

    Article  CAS  PubMed  Google Scholar 

  16. Brabb T, von Dassow P, Ordonez N, Schnabel B, Duke B, Goverman J. In situ tolerance within the central nervous system as a mechanism for preventing autoimmunity. J Exp Med. 2000;192:871–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Heimberger AB, Sampson JH. Immunotherapy coming of age: what will it take to make it standard of care for glioblastoma? Neuro Oncol. 2011;13:3–13.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Li W, Graeber MB. The molecular profile of microglia under the influence of glioma. Neuro Oncol. 2012;8:958–78.

    Article  CAS  Google Scholar 

  19. Quattrocchi KB, Miller CH, Cush S, Bernard SA, Dull ST, Smith M, et al. Pilot study of local autologous tumor infiltrating lymphocytes for the treatment of recurrent malignant gliomas. J Neuro Oncol. 1999;45:141–57.

    Article  CAS  Google Scholar 

  20. Gigliotti F, Lee D, Insel RA, Scheld WM. IgG penetration into the cerebrospinal fluid in a rabbit model of meningitis. J Infect Dis. 1987;156:394–8.

    Article  CAS  PubMed  Google Scholar 

  21. Stemmler H-J, Schmitt M, Willems A, Bernhard H, Harbeck N, Heinemann V. Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impairment of blood-brain barrier. Anticancer Drugs. 2007;18:23–8.

    Article  CAS  PubMed  Google Scholar 

  22. Sonabend AM, Rolle CE, Lesniak MS. The role of regulatory T cells in malignant glioma. Anticancer Res. 2008;28:1143–50.

    PubMed  Google Scholar 

  23. Kostianovsky AM, Maier LM, Anderson RC, Bruce JN, Anderson DE. Astrocytic regulation of human monocytic/microglial activation. J Immunol. 2008;181:5425–32.

    Article  CAS  PubMed  Google Scholar 

  24. Kennedy BC, Showers CR, Anderson DE, Anderson L, Canoll P, Bruce JN, et al. Tumor-associated macrophages in glioma: friend or foe? J Oncol. 2013;2013:486912.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Conti A, Gulì C, La Torre D, Tomasello C, Angileri FF, Aguennouz MH. Role of inflammation and oxidative stress mediators in gliomas. Cancer. 2010;2:693–712.

    Article  CAS  Google Scholar 

  26. Dunwiddie TV. The physiological role of adenosine in the central nervous system. Int Rev Neurobiol. 1985;27:63.

    Article  CAS  PubMed  Google Scholar 

  27. Dunn GP, Fecci PE, Curry WT. Cancer immunoediting in malignant glioma. Neurosurgery. 2012;71:201–23.

    Article  PubMed  Google Scholar 

  28. Anderson RC, Anderson DE, Elder JB, Brown MD, Mandigo CE, Parsa AT, et al. Lack of B7 expression, not human leukocyte antigen expression, facilitates immune evasion by human malignant gliomas. Neurosurgery. 2007;60:1129–36.

    Article  PubMed  Google Scholar 

  29. Badie B, Bartley B, Schartner J. Differential expression of MHC class II and B7 costimulatory molecules by microglia in rodent gliomas. J Neuroimmunol. 2002;133:39–45.

    Article  CAS  PubMed  Google Scholar 

  30. Schartner JM, Hagar AR, Van Handel M, Zhang L, Nadkarni N, Badie B. Impaired capacity for upregulation of MHC class II in tumor‐associated microglia. Glia. 2005;51:279–85.

    Article  PubMed  Google Scholar 

  31. Wintterle S, Schreiner B, Mitsdoerffer M, Schneider D, Chen L, Meyermann R, et al. Expression of the B7-related molecule B7-H1 by glioma cells a potential mechanism of immune paralysis. Cancer Res. 2003;63:7462–7.

    CAS  PubMed  Google Scholar 

  32. Kjellman C, Olofsson SP, Hansson O, Von Schantz T, Lindvall M, Nilsson I, et al. Expression of TGF‐β isoforms, TGF‐β receptors, and SMAD molecules at different stages of human glioma. Int J Cancer. 2000;89:251–8.

    Article  CAS  PubMed  Google Scholar 

  33. Li W, Graeber MB. The molecular profile of microglia under the influence of glioma. Neuro Oncol. 2012;14:958–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Merzak A, McCrea S, Koocheckpour S, Pilkington G. Control of human glioma cell growth, migration and invasion in vitro by transforming growth factor β1. Br J Cancer. 1994;70:199–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Payner T, Leaver HA, Knapp B, Whittle IR, Trifan OC, Miller S, et al. Microsomal prostaglandin E synthase-1 regulates human glioma cell growth via prostaglandin E2–dependent activation of type II protein kinase A. Mol Cancer Ther. 2006;5:1817–26.

    Article  CAS  PubMed  Google Scholar 

  36. Badie B, Schartner J. Role of microglia in glioma biology. Microsc Res Tech. 2001;54:106–13.

    Article  CAS  PubMed  Google Scholar 

  37. Jansen T, Tyler B, Mankowski JL, Recinos VR, Pradilla G, Legnani F, et al. FasL gene knock-down therapy enhances the antiglioma immune response. Neuro Oncol. 2010;12:482–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Wagner S, Czub S, Greif M, Vince GH, Süss N, Kerkau S, et al. Microglial/macrophage expression of interleukin 10 in human glioblastomas. Int J Cancer. 1999;82:12–6.

    Article  CAS  PubMed  Google Scholar 

  39. Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 2004;4:71–8.

    Article  CAS  PubMed  Google Scholar 

  40. Wainwright DA, Sengupta S, Han Y, Lesniak MS. Thymus-derived rather than tumor-induced regulatory T cells predominate in brain tumors. Neuro Oncol. 2011;13:1308–23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Mitsuka K, Kawataki T, Satoh E, Asahara T, Horikoshi T, Kinouchi H. Expression of indoleamine 2, 3-dioxygenase and correlation with pathological malignancy in gliomas. Neurosurgery. 2013;72:1031–9.

    Article  PubMed  Google Scholar 

  42. Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, et al. Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res. 2004;64:7011–21.

    Article  CAS  PubMed  Google Scholar 

  43. Wu A, Oh S, Gharagozlou S, Vedi RN, Ericson K, Low WC, et al. In vivo vaccination with tumor cell lysate plus CpG oligodeoxynucleotides eradicates murine glioblastoma. J Immunother. 2007;30:789–97.

    Article  CAS  PubMed  Google Scholar 

  44. Hatiboglu MA, Wei J, Wu ASG, Heimberger AB. Immune therapeutic targeting of glioma cancer stem cells. Target Oncol. 2010;5:217–27.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Ji B, Chen Q, Liu B, Wu L, Tian D, Guo Z, et al. Glioma stem cell-targeted dendritic cells as a tumor vaccine against malignant glioma. Yonsei Med J. 2013;54:92–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Badie B, Schartner JM. Flow cytometric characterization of tumor-associated macrophages in experimental gliomas. Neurosurgery. 2000;46:957–62.

    CAS  PubMed  Google Scholar 

  47. Komohara Y, Ohnishi K, Kuratsu J, Takeya M. Possible involvement of the M2 anti‐inflammatory macrophage phenotype in growth of human gliomas. J Pathol. 2008;216:15–24.

    Article  CAS  PubMed  Google Scholar 

  48. Rodrigues JC, Gonzalez GC, Zhang L, Ibrahim G, Kelly JJ, Gustafson MP, et al. Normal human monocytes exposed to glioma cells acquire myeloid-derived suppressor cell-like properties. Neuro Oncol. 2010;12:351–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Boehm UKT, Groot M, Howard JC. Cellular responses to interferon-gamma. Annu Rev Immunol. 1997;15:749–95.

    Article  CAS  PubMed  Google Scholar 

  50. Filipazzi P, Huber V, Rivoltini L. Phenotype, function and clinical implications of myeloid-derived suppressor cells in cancer patients. Cancer Immunol Immunother. 2012;61:255–63.

    Article  CAS  PubMed  Google Scholar 

  51. Lowther DE, Hafler DA. Regulatory T cells in the central nervous system. Immunol Rev. 2012;248:156–69.

    Article  PubMed  Google Scholar 

  52. 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;8:234–43.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Heimberger AB, Abou-Ghazal M, Reina-Ortiz C, Yang DS, Sun W, Qiao W, et al. Incidence and prognostic impact of FoxP3+ regulatory T cells in human gliomas. Clin Cancer Res. 2008;14:5166–72.

    Article  CAS  PubMed  Google Scholar 

  54. Sonabend AM, Dana K, Lesniak MS. Targeting epidermal growth factor receptor variant III: a novel strategy for the therapy of malignant glioma. Expert Rev Anticancer Ther. 2007;12:S45–50.

    Article  Google Scholar 

  55. Zhang L, Alizadeh D, Van Handel M, Kortylewski M, Yu H, Badie B. Stat3 inhibition activates tumor macrophages and abrogates glioma growth in mice. Glia. 2009;57:1458–67.

    Article  PubMed  Google Scholar 

  56. Schaefer LK, Menter DG, Schaefer TS. Activation of stat3 and stat1 DNA binding and transcriptional activity in human brain tumour cell lines by gp130 cytokines. Cell Signal. 2000;12:143–51.

    Article  CAS  PubMed  Google Scholar 

  57. Wang T, Niu G, Kortylewski M, Burdelya L, Shain K, Zhang S, et al. Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nat Med. 2004;10:48–54.

    Article  PubMed  CAS  Google Scholar 

  58. Sherry MM, Reeves A, Wu JK, Cochran BH. STAT3 is required for proliferation and maintenance of multipotency in glioblastoma stem cells. Stem Cells. 2009;27:2383–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Brantley EC, Benveniste EN. Signal transducer and activator of transcription-3: a molecular hub for signaling pathways in gliomas. Mol Cancer Res. 2008;6:675–84.

    Article  CAS  PubMed  Google Scholar 

  60. Mitchell DA, Cui X, Schmittling RJ, Sanchez-Perez L, Snyder DJ, Congdon KL, et al. Monoclonal antibody blockade of IL-2 receptor α during lymphopenia selectively depletes regulatory T cells in mice and humans. Blood. 2011;118:3003–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Sissons J, Carmichael A. Clinical aspects and management of cytomegalovirus infection. J Infect. 2002;44:78–83.

    Article  CAS  PubMed  Google Scholar 

  62. Cinatl J, Vogel JU, Kotchetkov R, Wilhelm DH. Oncomodulatory signals by regulatory proteins encoded by human cytomegalovirus: a novel role for viral infection in tumor progression. FEMS Microbiol Rev. 2004;28:59–77.

    Article  CAS  PubMed  Google Scholar 

  63. Kossmann T, Morganti-Kossmann MC, Orenstein JM, Britt WJ, Wahl SM, Smith PD. Cytomegalovirus production by infected astrocytes correlates with transforming growth factor-β release. J Infect Dis. 2003;187:534–41.

    Article  CAS  PubMed  Google Scholar 

  64. Reddehase MJ. The immunogenicity of human and murine cytomegaloviruses. Curr Opin Immunol. 2000;12:390–6.

    Article  CAS  PubMed  Google Scholar 

  65. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331:1565–70.

    Article  CAS  PubMed  Google Scholar 

  66. Ruiz J, Cotorruelo J, Tudela V, Ullate P, Val-Bernal F, de Francisco A, et al. Transmission of glioblastoma multiforme to two kidney transplant recipients from the same donor in the absence of ventricular shunt. Transplantation. 1993;55:682–3.

    Article  CAS  PubMed  Google Scholar 

  67. Pellegatta S, Cuppini L, Finocchiaro G. Brain cancer immunoediting: novel examples provided by immunotherapy of malignant gliomas. Expert Rev Anticancer Ther. 2011;11:1759–74.

    Article  CAS  PubMed  Google Scholar 

  68. Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat Med. 2004;10:909–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Dillman RO, Duma CM, Schiltz PM, DePriest C, Ellis RA, Okamoto K, et al. Intracavitary placement of autologous lymphokine-activated killer (LAK) cells after resection of recurrent glioblastoma. J Immunother. 2004;27:398–404.

    Article  PubMed  Google Scholar 

  70. Xu X, Stockhammer F, Schmitt M. Cellular-based immunotherapies for patients with glioblastoma multiforme. J Immunol Res. 2012;2012:764213.

    Google Scholar 

  71. Sonabend AM, Ogden AT, Maier LM, Anderson DE, Canoll P, Bruce JN, et al. Medulloblastoma: challenges for effective immunotherapy. J Neurooncol. 2012;108:1–10.

    Article  CAS  PubMed  Google Scholar 

  72. Sloan AE, Dansey R, Zamorano L, Barger G, Hamm C, Diaz F, et al. Adoptive immunotherapy in patients with recurrent malignant glioma: preliminary results of using autologous whole-tumor vaccine plus granulocyte-macrophage colony-stimulating factor and adoptive transfer of anti-CD3-activated lymphocytes. Neurosurg Focus. 2000;9:1–8.

    Article  Google Scholar 

  73. Wykosky J, Gibo DM, Stanton C, Debinski W. Interleukin-13 receptor α2, EphA2, and Fos-related antigen 1 as molecular denominators of high-grade astrocytomas and specific targets for combinatorial therapy. Clin Cancer Res. 2008;14(1):199–208.

    Article  CAS  PubMed  Google Scholar 

  74. Clavreul A, Piard N, Tanguy J-Y, Gamelin E, Rousselet M-C, Leynia P, et al. Autologous tumor cell vaccination plus infusion of GM-CSF by a programmable pump in the treatment of recurrent malignant gliomas. J Clin Neurosci. 2010;17(7):842–8.

    Article  CAS  PubMed  Google Scholar 

  75. Wu AWS, **ao J, et al. Expression of MHC I and NK ligands on human CD1331 glioma cells: possible targets of immunotherapy. J Neurooncol. 2007;82(2):121–31.

    Article  CAS  Google Scholar 

  76. Sobol R, Fakhrai H, Shawler D, Gjerset R, Dorigo O, Carson C, et al. Interleukin-2 gene therapy in a patient with glioblastoma. Gene Ther. 1995;2(2):164–7.

    CAS  PubMed  Google Scholar 

  77. Okada H, Lieberman FS, Edington HD, Witham TF, Wargo MJ, Cai Q, et al. Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of recurrent glioblastoma: preliminary observations in a patient with a favorable response to therapy. J Neurooncol. 2003;64(1):13–20.

    Article  PubMed  Google Scholar 

  78. Parney IF, Chang L-J, Farr-Jones MA, Hao C, Smylie M, Petruk KC. Technical hurdles in a pilot clinical trial of combined B7-2 and GM-CSF immunogene therapy for glioblastomas and melanomas. J Neurooncol. 2006;78:71–80.

    Article  CAS  PubMed  Google Scholar 

  79. Andrews DW, Resnicoff M, Flanders AE, Kenyon L, Curtis M, Merli G, et al. Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas. J Clin Oncol. 2001;19:2189–200.

    CAS  PubMed  Google Scholar 

  80. Steiner HH, Bonsanto MM, Beckhove P, Brysch M, Geletneky K, Ahmadi R, et al. Antitumor vaccination of patients with glioblastoma multiforme: a pilot study to assess feasibility, safety, and clinical benefit. J Clin Oncol. 2004;22:4272–81.

    Article  PubMed  Google Scholar 

  81. Yu JS, Wheeler CJ, Zeltzer PM, Ying H, Finger DN, Lee PK, et al. Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial T-cell infiltration. Cancer Res. 2001;61(3):842–7.

    CAS  PubMed  Google Scholar 

  82. Steinman RM, Banchereau J. Taking dendritic cells into medicine. Nature. 2007;449(7161):419–26.

    Article  CAS  PubMed  Google Scholar 

  83. Yu JS, Liu G, Ying H, Yong WH, Black KL, Wheeler CJ. Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma. Cancer Res. 2004;64(14):4973–9.

    Article  CAS  PubMed  Google Scholar 

  84. Prins RM, Soto H, Konkankit V, Odesa SK, Eskin A, Yong WH, et al. Gene expression profile correlates with T-cell infiltration and relative survival in glioblastoma patients vaccinated with dendritic cell immunotherapy. Clin Cancer Res. 2011;17(6):1603–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Wheeler CJ, Black KL, Liu G, Mazer M, Zhang X-X, Pepkowitz S, et al. Vaccination elicits correlated immune and clinical responses in glioblastoma multiforme patients. Cancer Res. 2008;68(14):5955–64.

    Article  CAS  PubMed  Google Scholar 

  86. Okada H, Kalinski P, Ueda R, Hoji A, Kohanbash G, Donegan TE, et al. Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with α-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma. J Clin Oncol. 2011;29(3):330–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Ardon H, Gool SV, Lopes IS, et al. Integration of autologous dendritic cell-based immunotherapy in the primary treatment for patients with newly diagnosed glioblastoma multiforme: a pilot study. J Neurooncol. 2010;99(2):261–72.

    Article  CAS  PubMed  Google Scholar 

  88. Sampson JH, Archer GE, Mitchell DA, et al. An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme. Mol Cancer Ther. 2009;8(10):2773–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. De Vleeschouwer S, Fieuws S, Rutkowski S, Van Calenbergh F, Van Loon J, Goffin J, et al. Postoperative adjuvant dendritic cell-based immunotherapy in patients with relapsed glioblastoma multiforme. Clin Cancer Res. 2008;14(10):3098–104.

    Google Scholar 

  90. Yamanaka R, Homma J, Yajima N, Tsuchiya N, Sano M, Kobayashi T, et al. Clinical evaluation of dendritic cell vaccination for patients with recurrent glioma: results of a clinical phase I/II trial. Clin Cancer Res. 2005;11(11):4160–7.

    Article  CAS  PubMed  Google Scholar 

  91. Liau LM, Prins RM, Kiertscher SM, et al. Dendritic cell vaccination in glioblastoma patients induces systemic and intracranial T-cell responses modulated by the local central nervous system tumor microenvironment. Clin Cancer Res. 2005;11(15):5515–25.

    Article  CAS  PubMed  Google Scholar 

  92. Kikuchi T, Akasaki Y, Abe T, et al. Vaccination of glioma patients with fusions of dendritic and glioma cells and recombinant human interleukin 12. J Immunother. 2004;27(6):452–9.

    Article  CAS  PubMed  Google Scholar 

  93. Caruso LM, Orme AM, Neale AM, et al. Results of a phase 1 study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children and young adults with brain cancer. Neuro Oncol. 2004;6(3):236–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Wheeler CJ, Das A, Liu G, Yu JS, Black KL. Clinical responsiveness of glioblastoma multiforme to chemotherapy after vaccination. Clin Cancer Res. 2004;10(16):5316–26.

    Article  CAS  PubMed  Google Scholar 

  95. Yamanaka R, Abe T, Yajima N, et al. Vaccination of recurrent glioma patients with tumour lysate-pulsed dendritic cells elicits immune responses: results of a clinical phase I/II trial. Br J Cancer. 2003;89(7):1172–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Fadul CE, Fisher JL, Hampton TH, Lallana EC, Li Z, Gui J, et al. Immune response in patients with newly diagnosed glioblastoma multiforme treated with intranodal autologous tumor lysate-dendritic cell vaccination after radiation chemotherapy. J Immunother. 2011;34:382.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Ardon H, De Vleeschouwer S, Van Calenbergh F, Claes L, Kramm CM, Rutkowski S, et al. Adjuvant dendritic cell‐based tumour vaccination for children with malignant brain tumours. Pediatr Blood Cancer. 2010;54:519–25.

    PubMed  Google Scholar 

  98. Prins RM, Wang X, Soto H, Young E, Lisiero DN, Fong B, et al. Comparison of glioma-associated antigen peptide-loaded versus autologous tumor lysate-loaded dendritic cell vaccination in malignant glioma patients. J Immunother. 2013;36(2):152–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Moscatello DK, Ramirez G, Wong AJ. A naturally occurring mutant human epidermal growth factor receptor as a target for peptide vaccine immunotherapy of tumors. Cancer Res. 1997;57(8):1419–24.

    CAS  PubMed  Google Scholar 

  100. Lateef SS, Gupta S, Jayathilaka LP, Krishnanchettiar S, Huang J-S, Lee B-S. An improved protocol for coupling synthetic peptides to carrier proteins for antibody production using DMF to solubilize peptides. J Biomol Tech. 2007;18:173.

    PubMed  PubMed Central  Google Scholar 

  101. Chang DZ, Lomazow W, Joy Somberg C, Stan R, Perales M-A. Granulocyte-macrophage colony stimulating factor: an adjuvant for cancer vaccines. Hematology. 2004;9(3):207–15.

    Article  CAS  PubMed  Google Scholar 

  102. Aparicio S, Caldas C. The implications of clonal genome evolution for cancer medicine. N Engl J Med. 2013;368:842–51.

    Article  CAS  PubMed  Google Scholar 

  103. Cheever MA, Allison JP, Ferris AS, Finn OJ, Hastings BM, Hecht TT, et al. The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research. Clin Cancer Res. 2009;15:5323–37.

    Article  PubMed  Google Scholar 

  104. Ekstrand AJ, James CD, Cavenee WK, Seliger B, Pettersson RF, Collins VP. Genes for epidermal growth factor receptor, transforming growth factor α, and epidermal growth factor and their expression in human gliomas in vivo. Cancer Res. 1991;51:2164–72.

    CAS  PubMed  Google Scholar 

  105. Lallier TE. Cell lineage and cell migration in the neural crest. Ann N Y Acad Sci. 1991;615:158–71.

    Article  CAS  PubMed  Google Scholar 

  106. Kuramoto T. Detection of MAGE-1 tumor antigen in brain tumor. Kurume Med J. 1996;44:43–51.

    Article  Google Scholar 

  107. Sasaki M, Nakahira K, Kawano Y, Katakura H, Yoshimine T, Shimizu K, et al. MAGE-E1, a new member of the melanoma-associated antigen gene family and its expression in human glioma. Cancer Res. 2001;61:4809–14.

    CAS  PubMed  Google Scholar 

  108. Kurpad SN, Wikstrand CJ, Batra SK, McLendon RE, Bigner DD. Tumor antigens in astrocytic gliomas. Glia. 1995;15:244–56.

    Article  CAS  PubMed  Google Scholar 

  109. Okada H, Kohanbash G, Zhu X, Kastenhuber ER, Hoji A, Ueda R, et al. Immunotherapeutic approaches for glioma. Crit Rev Immunol. 2009;29(1):1–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Liu G, Yu JS, Zeng G, et al. AIM-2: a novel tumor antigen is expressed and presented by human glioma cells. J Immunother. 2004;27(3):220–6.

    Article  CAS  PubMed  Google Scholar 

  111. Abdouh M, Facchino S, Chatoo W, Balasingam V, Ferreira J, Bernier G. BMI1 sustains human glioblastoma multiforme stem cell renewal. J Neurosci. 2009;29(28):8884–96.

    Article  CAS  PubMed  Google Scholar 

  112. Shono T, Tofilon PJ, Bruner JM, Owolabi O, Lang FF. Cyclooxygenase-2 expression in human gliomas: prognostic significance and molecular correlations. Cancer Res. 2001;61(11):4375–81.

    CAS  PubMed  Google Scholar 

  113. Saikali S, Avril T, Collet B, Hamlat A, Bansard J-Y, Drenou B, et al. Expression of nine tumour antigens in a series of human glioblastoma multiforme: interest of EGFRvIII, IL-13Rα2, gp100 and TRP-2 for immunotherapy. J Neurooncol. 2007;81(2):139–48.

    Article  CAS  PubMed  Google Scholar 

  114. Driggers L, Zhang JG, Newcomb EW, Ge L, Hoa N, Jadus MR. Immunotherapy of pediatric brain tumor patients should include an immunoprevention strategy: a medical hypothesis paper. J Neurooncol. 2010;97(2):159–69.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Orzan F, Pellegatta S, Poliani PL, et al. Enhancer of Zeste 2 (EZH2) is up-regulated in malignant gliomas and in glioma stem-like cells. Neuropathol Appl Neurobiol. 2011;37(4):381–94.

    Article  CAS  PubMed  Google Scholar 

  116. Cheng L, Wu Q, Guryanova OA, et al. Elevated invasive potential of glioblastoma stem cells. Biochem Biophys Res Commun. 2011;406(4):643–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. ** F, Zhao L, Guo YJ, et al. Influence of Etoposide on anti-apoptotic and multidrug resistance-associated protein genes in CD133 positive U251 glioblastoma stem-like cells. Brain Res. 2010;1336:103–11.

    Article  CAS  PubMed  Google Scholar 

  118. Kuan CT, Wakiya K, Herndon JE, et al. MRP3: a molecular target for human glioblastoma multiforme immunotherapy. BMC Cancer. 2010;10:468.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  119. Ishiwata T, Teduka K, Yamamoto T, Kawahara K, Matsuda Y, Naito Z. Neuroepithelial stem cell marker nestin regulates the migration, invasion and growth of human gliomas. Oncol Rep. 2011;26:91–9.

    Google Scholar 

  120. Ligon KL, Alberta JA, Kho AT, et al. The oligodendroglial lineage marker OLIG2 is universally expressed in diffuse gliomas. J Neuropathol Exp Neurol. 2004;63(5):499–509.

    CAS  PubMed  Google Scholar 

  121. Xu G, et al. Adenoviral-mediated interleukin-18 expression in mesenchymal stem cells effectively suppresses the growth of glioma in rats. Cell Biol Int. 2009;33(4):466–74.

    Article  CAS  PubMed  Google Scholar 

  122. Zhang JG, Kruse CA, Driggers L, et al. Tumor antigen precursor protein profiles of adult and pediatric brain tumors identify potential targets for immunotherapy. J Neurooncol. 2008;88(1):65–76.

    Article  PubMed  PubMed Central  Google Scholar 

  123. Rossi M, Magnoni L, Miracco C, et al. β-catenin and Glil are prognostic markers in glioblastoma. Cancer Biol Ther. 2011;11(8):753–61.

    Article  PubMed  Google Scholar 

  124. Cui D, Xu Q, Wang K, Che X. Gli1 is a potential target for alleviating multidrug resistance of gliomas. J Neurol Sci. 2010;288(1–2):156–66.

    Article  CAS  PubMed  Google Scholar 

  125. Senetta R, Miracco C, Lanzafame S, et al. Epidermal growth factor receptor and caveolin-1 coexpression identifies adult supratentorial ependymomas with rapid unfavorable outcomes. Neuro Oncol. 2011;13(2):176–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Sivaparvathi M, Sawaya R, Wang SW, et al. Overexpression and localization of cathepsin B during the progression of human gliomas. Clin Exp Metastasis. 1995;13(1):49–56.

    Article  CAS  PubMed  Google Scholar 

  127. Kitange GJ, Carlson BL, Schroeder MA, et al. Expression of CD74 in high-grade gliomas: a potential role in temozolomide resistance. J Neurooncol. 2010;100(2):177–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Lewis-Tuffin LJ, Rodriguez F, Giannini C, et al. Misregulated E-cadherin expression associated with an aggressive brain tumor phenotype. PLoS One. 2010;5(10):e13665.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  129. Scarcella DL, Chow CW, Gonzales MF, Economou C, Brasseur F, Ashley DM. Expression of MAGE and GAGE in high-grade brain tumors: a potential target for specific immunotherapy and diagnostic markers. Clin Cancer Res. 1999;5(2):335–41.

    CAS  PubMed  Google Scholar 

  130. Mennel HD, Lell B. Ganglioside (GD2) expression and intermediary filaments in astrocytic tumors. Clin Neuropathol. 2005;24(1):13–8.

    CAS  PubMed  Google Scholar 

  131. Yamamoto H, Swoger J, Greene S, et al. β1,6-N-acethylglucosamine-bearing N-glycans in human gliomas: implications for a role in regulating invasivity. Cancer Res. 2000;60(1):134–42.

    CAS  PubMed  Google Scholar 

  132. Kogiku M, Ohsawa I, Matsumoto K, et al. Prognosis of glioma patients by combined immunostaining for survivin, Ki-67 and epidermal growth factor receptor. J Clin Neurosci. 2008;15(11):1198–203.

    Article  CAS  PubMed  Google Scholar 

  133. Persson O, Salford LG, Fransson J, Widegren B, Borrebaeck CAK, Holmqvist B. Distribution, cellular localization, and therapeutic potential of the tumor-associated antigen Ku70/80 in glioblastoma multiforme. J Neurooncol. 2010;97(2):207–15.

    Article  CAS  PubMed  Google Scholar 

  134. Bao L, Dunham K, Lucas K. MAGE-A1, MAGEA3, and NY-ESO-1 can be upregulated on neuroblastoma cells to facilitate cytotoxic T lymphocyte-mediated tumor cell killing. Cancer Immunol Immunother. 2011;60(9):1299–307.

    Article  CAS  PubMed  Google Scholar 

  135. Jian JG, Eguchi J, Kruse CA, et al. Antigenic profiling of glioma cells to generate allogeneic vaccines or dendritic cellbased therapeutics. Clin Cancer Res. 2007;13(2):566–75.

    Article  Google Scholar 

  136. Elsir T, Eriksson A, Orrego A, Lindström MS, Nisté M. Expression of PROX1 is a common feature of high grade malignant astrocytic gliomas. J Neuropathol Exp Neurol. 2010;69(2):129–38.

    Article  CAS  PubMed  Google Scholar 

  137. Geiger KD, Hendruschk S, Rieber EP, et al. The prostate stem cell antigen represents a novel glioma-associated antigen. Oncol Rep. 2011;26(1):13–21.

    CAS  PubMed  Google Scholar 

  138. Ferletta M, Uhrbom L, Olofsson T, Pontén F, Westermark B. Sox10 has a broad expression pattern in gliomas and enhances platelet-derived growth factor-B—induced gliomagenesis. Mol Cancer Res. 2007;5(9):891–7.

    Article  CAS  PubMed  Google Scholar 

  139. Schmitz M, Wehner R, Stevanovic S, et al. Identification of a naturally processed T cell epitope derived from the glioma associated protein SOX11. Cancer Lett. 2007;245(1–2):331–6.

    Article  CAS  PubMed  Google Scholar 

  140. Gondi CS, Lakka SS, Dinh DH, Olivero WC, Gujrati M, Rao JS. RNAi-mediated inhibition of cathepsin B and uPAR leads to decreased cell invasion, angiogenesis and tumor growth in gliomas. Oncogene. 2004;23(52):8486–96.

    Article  CAS  PubMed  Google Scholar 

  141. Ueda R, Low KL, Zhu X, et al. Spontaneous immune responses against glioma-associated antigens in a long term survivor with malignant glioma. J Transl Med. 2007;5:68.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Wykosky J, Gibo DM, Stanton C, Debinski W. EphA2 as a novel molecular marker and target in glioblastoma multiforme. Mol Cancer Res. 2005;3:541–51.

    Article  CAS  PubMed  Google Scholar 

  143. Ekstrand AJ, Longo N, Hamid ML, Olson JJ, Liu L, Collins VP, et al. Functional characterization of an EGF receptor with a truncated extracellular domain expressed in glioblastomas with EGFR gene amplification. Oncogene. 1994;9:2313–20.

    CAS  PubMed  Google Scholar 

  144. Heimberger AB, Hlatky R, Suki D, Yang D, Weinberg J, Gilbert M, et al. Prognostic effect of epidermal growth factor receptor and EGFRvIII in glioblastoma multiforme patients. Clin Cancer Res. 2005;11(4):1462–6.

    Article  CAS  PubMed  Google Scholar 

  145. Choi KSC, Sampson JH. Tumors of the central nervous system. In: Hayat MA, editor. Tumors of the central nervous system, vol. 1. Dordrecht: Springer Netherlands; 2011.

    Google Scholar 

  146. Heimberger AB, Hussain S, Aldape K, Sawaya R, Archer G, Friedman H, et al. Tumor-specific peptide vaccination in newly-diagnosed patients with GBM. J Clin Oncol. 2006;24 Suppl 18:2529.

    Google Scholar 

  147. Schmittling RJ, Archer GE, Mitchell DA, Heimberger A, Pegram C, Herndon II JE, et al. Detection of humoral response in patients with glioblastoma receiving EGFRvIII-KLH vaccines. J Immunol Methods. 2008;339:74–81.

    Article  CAS  PubMed  Google Scholar 

  148. Sampson J, Archer G, Bigner D, Davis T, Friedman H, Keler T, et al. Effect of EGFRvIII-targeted vaccine (CDX-110) on immune response and TTP when given with simultaneous standard and continuous temozolomide in patients with GBM. J Clin Oncol. 2008;26 Suppl 15:2011.

    Google Scholar 

  149. De Maio A. Heat shock proteins: facts, thoughts, and dreams. Shock. 1999;11:1–12.

    Article  PubMed  Google Scholar 

  150. Nishikawa M, Takemoto S, Takakura Y. Heat shock protein derivatives for delivery of antigens to antigen presenting cells. Int J Pharm. 2008;354:23–7.

    Article  CAS  PubMed  Google Scholar 

  151. Belli F, Testori A, Rivoltini L, Maio M, Andreola G, Sertoli MR, et al. Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: clinical and immunologic findings. J Clin Oncol. 2002;20:4169–80.

    Article  CAS  PubMed  Google Scholar 

  152. Bogdahn PH, Stockhammer G, et al. Targeted therapy for high-grade glioma with the TGF-βeta2 inhibitor trabedersen: results of a randomized and controlled phase IIb study. Neuro Oncol. 2011;13(1):132–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Yang I, Fang S, Parsa AT. Heat shock proteins in glioblastomas. Neurosurg Clin N Am. 2010;21:111–23.

    Article  PubMed  Google Scholar 

  154. Crane CA, Han SJ, Ahn B, Oehlke J, Kivett V, Fedoroff A, et al. Individual patient-specific immunity against high-grade glioma after vaccination with autologous tumor derived peptides bound to the 96 KD chaperone protein. Clin Cancer Res. 2013;19(1):205–14.

    Article  CAS  PubMed  Google Scholar 

  155. Jaschinski TR, Jachimczak P, Seitz C, Schneider A, Schlingensiepen KH. The antisense oligonucleotide trabedersen (AP 12009) for the targeted inhibition of TGF-βeta2. Curr Pharm Biotechnol. 2011;12:2203–13.

    Article  CAS  PubMed  Google Scholar 

  156. Morantz RA, Wood GW, Foster M, Clark M, Gollahon K. Macrophages in experimental and human brain tumors: part 2: studies of the macrophage content of human brain tumors. J Neurosurg. 1979;50:305–11.

    Article  CAS  PubMed  Google Scholar 

  157. Morse JH, Turcotte JG, Merion RM, Campbell Jr DA, Burtch GD, Lucey MR. Development of a malignant tumor in a liver transplant graft procured from a donor with a cerebral neoplasm. Transplantation. 1990;50:875–6.

    Article  CAS  PubMed  Google Scholar 

  158. Buckner JC, Schomberg PJ, McGinnis WL, Cascino TL, Scheithauer BW, O’Fallon JR, et al. A phase III study of radiation therapy plus carmustine with or without recombinant interferon‐α in the treatment of patients with newly diagnosed high‐grade glioma. Cancer. 2001;92(2):420–33.

    Article  CAS  PubMed  Google Scholar 

  159. Olson JJ, McKenzie E, Skurski-Martin M, Zhang Z, Brat D, Phuphanich S. Phase I analysis of BCNU-impregnated biodegradable polymer wafers followed by systemic interferon alfa-2b in adults with recurrent glioblastoma multiforme. J Neurooncol. 2008;90(3):293–9.

    Article  CAS  PubMed  Google Scholar 

  160. Tabatabai G, Frank B, Möhle R, Weller M, Wick W. Irradiation and hypoxia promote homing of haematopoietic progenitor cells towards gliomas by TGF-β-dependent HIF-1α-mediated induction of CXCL12. Brain. 2006;129:2426–35.

    Article  PubMed  Google Scholar 

  161. Ehrhart PS, Tsang MLS, Carroll AG, Barcellos-Hoff MH. Latent transforming growth factor β1 activation in situ: quantitative and functional evidence after low-dose γ-irradiation. FASEB J. 1997;11:991–1002.

    CAS  PubMed  Google Scholar 

  162. Schlingensiepen KH, Jaschinski F, Lang SA, Moser C, Geissler EK, Schlitt HJ, et al. Transforming growth factor‐beta 2 gene silencing with trabedersen (AP 12009) in pancreatic cancer. Cancer Sci. 2011;102(6):1193–200.

    Article  CAS  PubMed  Google Scholar 

  163. Gansbacher B, Zier K, Daniels B, Cronin K, Bannerji R, Gilboa E. Interleukin 2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity. J Exp Med. 1990;172:1217–24.

    Article  CAS  PubMed  Google Scholar 

  164. Colombo F, Barzon L, Franchin E, Pacenti M, Pinna V, Danieli D, et al. Combined HSV-TK/IL-2 gene therapy in patients with recurrent glioblastoma multiforme: biological and clinical results. Cancer Gene Ther. 2005;12:835–48.

    Article  CAS  PubMed  Google Scholar 

  165. Fecci PE, Sweeney AE, Grossi PM, Nair SK, Learn CA, Mitchell DA, et al. Systemic anti-CD25 monoclonal antibody administration safely enhances immunity in murine glioma without eliminating regulatory T cells. Clin Cancer Res. 2006;12(14):4294–305.

    Article  CAS  PubMed  Google Scholar 

  166. Kohm AP, McMahon JS, Podojil JR, Begolka WS, DeGutes M, Kasprowicz DJ, et al. Cutting edge: anti-CD25 monoclonal antibody injection results in the functional inactivation, not depletion, of CD4+ CD25+ T regulatory cells. J Immunol. 2006;176:3301–5.

    Article  CAS  PubMed  Google Scholar 

  167. Jacobs JF, Punt CJ, Lesterhuis WJ, Sutmuller RP, Brouwer HM-H, Scharenborg NM, et al. Dendritic cell vaccination in combination with anti-CD25 monoclonal antibody treatment: a phase I/II study in metastatic melanoma patients. Clin Cancer Res. 2010;16:5067–78.

    Article  CAS  PubMed  Google Scholar 

  168. Sampson JH, Schmittling RJ, Archer GE, Congdon KL, Nair SK, Reap EA, et al. A pilot study of IL-2Rα blockade during lymphopenia depletes regulatory T-cells and correlates with enhanced immunity in patients with glioblastoma. PLoS One. 2012;7:e31046.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. The Gabriele Bartoli Brain Tumor Research Laboratory, Department of Neurological Surgery, The Neurological Institute, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA

    Adam M. Sonabend MD, Christopher R. Showers BS & Richard C. E. Anderson MD

  2. Department of Neurological Surgery, Columbia University Medical Center, New York, NY, USA

    Christopher R. Showers BS

  3. Department of Neurological Surgery, Morgan Stanley Children’s Hospital of New York Presbyterian, New York, NY, USA

    Richard C. E. Anderson MD

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  1. Adam M. Sonabend MD
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Correspondence to Adam M. Sonabend MD .

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  1. Children's Medical Center, Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran

    Nima Rezaei

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Sonabend, A.M., Showers, C.R., Anderson, R.C.E. (2015). Immunopathology and Immunotherapy of Central Nervous System Cancer. In: Rezaei, N. (eds) Cancer Immunology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-46410-6_18

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