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Neuroscience Bulletin logoLink to Neuroscience Bulletin
. 2008 Feb 27;24(1):39–44. doi: 10.1007/s12264-008-1107-1

Dendritic cell-based immunotherapy for malignant glioma

恶性神经胶质瘤的树突细胞免疫疗法

Jin-Hai Gu 1, Gang Li 1,
PMCID: PMC5552522  PMID: 18273075

Abstract

The immunotherapy for malignant glioma faces unique difficult, due to some anatomical and immunological characteristics including the existence of blood brain barrier, the absence of lymphatic tissues and dendritic cells (DCs) in the central nervous system (CNS) parenchyma, and the presence of an immunosuppressive microenvironment. Therefore, immunotherapeutic approaches will not be beneficial unless the compromised immune status in malignant glioma patients is overcome. DC-based immunotherapy, vaccinating cancer patients with DCs pulsed with various tumor antigens, is one of the most promising immunotherapeutic approaches for treatment of malignant glioma because it seems able to overcome, at least partially, the immunosuppressive state associated with primary malignancies. The preparation of DCs, choice of antigen, and route and schedule of administration are improving and optimizing with rapid development of molecular biology and gene engineering technology. DC vaccination in humans, after a number of pre-clinical models and clinical trials, would increase the clinical benefits for malignant glioma immunotherapy.

Keywords: dendritic cell, immunotherapy, malignant glioma

References

  • [1].Cartmell T., Southgate T., Rees G.S., Castro M.G., Lowenstein P.R., Luheshi G.N. Interleukin-1 mediates a rapid inflammatory response after injection of adenoviral vectors into the brain. J Neurosci. 1999;19:1517–1523. doi: 10.1523/JNEUROSCI.19-04-01517.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [2].Harling-Berg C.J., Park T.J., Knopf P.M. Role of the cervical lymphatics in the Th2-type hierarchy of CNS immune regulation. J Neuroimmunol. 1999;101:111–127. doi: 10.1016/S0165-5728(99)00130-7. [DOI] [PubMed] [Google Scholar]
  • [3].Perry V.H. A revised view of the central nervous system microenvironment and major histocompatibility complex class II antigen presentation. J Neuroimmunol. 1998;90:113–121. doi: 10.1016/S0165-5728(98)00145-3. [DOI] [PubMed] [Google Scholar]
  • [4].Stevenson P.G., Freeman S., Bangham C.R., Hawke S. Virus dissemination through the brain parenchyma without immunologic control. J Immunol. 1997;159:1876–1884. [PubMed] [Google Scholar]
  • [5].Thomas C.E., Schiedner G., Kochanek S., Castro M.G., Lowenstein P.R. Peripheral infection with adenovirus causes unexpected long-term brain inflammation in animals injected intracranially with first-generation, but not with high-capacity, adenovirus vectors: toward realistic long-term neurological gene therapy for chronic diseases. Proc Nat Acad Sci USA. 2000;97:7482–7487. doi: 10.1073/pnas.120474397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [6].Ransohoff R.M., Kivisakk P., Kidd G. Three or more routes for leukocyte migration into the central nervous system. Nat Rev Immunol. 2003;3:569–581. doi: 10.1038/nri1130. [DOI] [PubMed] [Google Scholar]
  • [7].Perry V.H., Andersson P.B. The inflammatory response in the CNS. Neuropathol Appl Neurobiol. 1992;18:454–459. doi: 10.1111/j.1365-2990.1992.tb00811.x. [DOI] [PubMed] [Google Scholar]
  • [8].Lowenstein P.R. Immunology of viral-vector-mediated gene transfer into the brain: an evolutionary and developmental perspective. Trends Immunol. 2002;23:23–30. doi: 10.1016/S1471-4906(01)02063-4. [DOI] [PubMed] [Google Scholar]
  • [9].Aloisi F., Ria F., Adorini L. Regulation of T-cell responses by CNS antigen-presenting cells: different roles for microglia and astrocytes. Immunol Today. 2000;21:141–147. doi: 10.1016/S0167-5699(99)01512-1. [DOI] [PubMed] [Google Scholar]
  • [10].Banchereau J., Steinman R.M. Dendritic cells and the control of immunity. Nature. 1998;392:245–252. doi: 10.1038/32588. [DOI] [PubMed] [Google Scholar]
  • [11].Dix A.R., Brooks W.H., Roszman T.L., Morford L.A. Immune defects observed in patients with primary malignant brain tumors. J Neuroimmunol. 1999;100:216–232. doi: 10.1016/S0165-5728(99)00203-9. [DOI] [PubMed] [Google Scholar]
  • [12].Zuber P., Kuppner M.C., 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. doi: 10.1002/eji.1830181023. [DOI] [PubMed] [Google Scholar]
  • [13].Pollack I.F., Okada H., Chambers W.H. Exploitation of immune mechanisms in the treatment of central nervous system cancer. Semin Pediatr Neurol. 2000;7:131–143. doi: 10.1053/pb.2000.6691. [DOI] [PubMed] [Google Scholar]
  • [14].Zeid N.A., Muller H.K. S100 positive dendritic cells in human lung tumors associated with cell differentiation and enhanced survival. Pathology. 1993;25:338–343. doi: 10.3109/00313029309090853. [DOI] [PubMed] [Google Scholar]
  • [15].Liau L.M., Black K.L., Prins R.M., Sykes S.N., DiPatre P.L., Cloughesy T.F., et al. Treatment of intracranial gliomas with bone marrow-derived dendritic cells pulsed with tumor antigens. J Neurosurg. 1999;90:1115–1124. doi: 10.3171/jns.1999.90.6.1115. [DOI] [PubMed] [Google Scholar]
  • [16].Yu J.S., Wheeler C.J., Zeltzer P.M., Ying H., Finger D.N., Lee P.K., et al. Vaccination of malignant glioma patients with peptide-pulsed dendritic cells elicits systemic cytotoxicity and intracranial T-cell infiltration. Cancer Res. 2001;61:842–847. [PubMed] [Google Scholar]
  • [17].Heimberger A.B., Crotty L.E., Archer G.E., McLendon R.E., Friedman A., Dranoff G., et al. Bone marrow-derived dendritic cells pulsed with tumor homogenate induce immunity against syngeneic intracerebral glioma. J Neuroimmunol. 2000;103:16–25. doi: 10.1016/S0165-5728(99)00172-1. [DOI] [PubMed] [Google Scholar]
  • [18].Yamanaka R., Zullo S.A., Tanaka R., Blaese M., Xanthopoulos K. Enhancement of antitumor immune response in glioma models in mice by genetically modified dendritic cells pulsed with Semiliki Forest virus-mediated complementary DNA. J Neurosurg. 2001;94:474–481. doi: 10.3171/jns.2001.94.3.0474. [DOI] [PubMed] [Google Scholar]
  • [19].Akasaki Y., Kikuchi T., Homma S., Abe T., Kofe D., Ohno T. Antitumor effect of immunizations with fusions of dendritic and glioma cells in a mouse brain tumor model. J Immunother. 2001;24:106–113. doi: 10.1097/00002371-200103000-00004. [DOI] [PubMed] [Google Scholar]
  • [20].Ni H., Spellman S.R., Jean W.C., Hall W.A., Low W.C. Immunization with dendritic cells pulsed with tumor extract increases survival of mice bearing intracranial gliomas. J Neurooncol. 2001;51:1–9. doi: 10.1023/A:1006452726391. [DOI] [PubMed] [Google Scholar]
  • [21].Liau L.M., Black K.L., Martin N.A., Sykes S.N., Bronstein J.M., Jouben-Steele L., et al. Treatment of a glioblastoma patient by vaccination with autologous dendritic cells pulsed with allogeneic major histocompatibility complex class I-matched tumor peptides. Neurosurg Focus. 2000;9:e8. doi: 10.3171/foc.2000.9.6.9. [DOI] [PubMed] [Google Scholar]
  • [22].Siesjö P., Visse E., Sjogren H.O. Cure of established, intracerebral rat gliomas induced by therapeutic immunizations with tumor cells and purified APC or adjuvant IFN-γ treatment. J Immunother Emphasis Tumor Immunol. 1996;19:334–345. [PubMed] [Google Scholar]
  • [23].Ferlazzo G., Klein J., Paliard X., Wei W.Z., Galy A. Dendriticcells generated from CD34+ progenitor cells with flt3 ligand, c-kit ligand, GM-CSF, IL-4, and TNF-alpha are functional antigen-presenting cells resembling mature monocytederived dendritic cells. J Immunother. 2000;23:48–58. doi: 10.1097/00002371-200001000-00007. [DOI] [PubMed] [Google Scholar]
  • [24].Labeur M.S., Roters B., Pers B., Mehling A., Luger T.A., Schwarz T., et al. Generation of tumor immunity by bone marrow-derived dendritic cells correlates with dendritic cell maturation stage. J Immunol. 1999;162:168–175. [PubMed] [Google Scholar]
  • [25].Schreurs M.W., Eggert A.A., Punt C.J., Figdor C.G., Adema G.J. Dendritic cell-based vaccines: from mouse models to clinical cancer immunotherapy. Crit Rev Oncog. 2000;11:1–17. [PubMed] [Google Scholar]
  • [26].Thurner B., Roder C., Dieckmann D., Heuer M., Kruse M., Glaser A., et al. Generation of large numbers of fully mature and stable dendritic cells from leukapheresis products for clinical application. J Immunol Methods. 1999;223:1–15. doi: 10.1016/S0022-1759(98)00208-7. [DOI] [PubMed] [Google Scholar]
  • [27].Fong L., Hou Y., Rivas A., Benike C., Yuen A., Fisher G.A., et al. Altered peptide ligand vaccination with Flt3 ligand expanded dendritic cells for tumor immunotherapy. Proc Natl Acad Sci USA. 2001;98:8809–8814. doi: 10.1073/pnas.141226398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [28].Yu J.S., Wheeler C.J., Zeltzer P.M. Dendritic cell immunotherapy for patients with glioblastoma multiforme and anaplastic astrocytoma. Proc Am Assoc Cancer Res. 2001;42:1478. [Google Scholar]
  • [29].Kirk C.J., Mule J.J. Gene-modified dendritic cells for use in tumor vaccines. Hum Gene Ther. 2000;11:797–806. doi: 10.1089/10430340050015419. [DOI] [PubMed] [Google Scholar]
  • [30].Jenne L., Schuler G., Steinkasserer A. Viral vectors for dendritic cell-based immunotherapy. Trends Immunol. 2001;22:102–107. doi: 10.1016/S1471-4906(00)01813-5. [DOI] [PubMed] [Google Scholar]
  • [31].Chi D.D., Merchant R.E., Rand R., Conrad A.J., Garrison D., Turner R., et al. Molecular detection of tumor-associated antigens shared by human cutaneous melanomas and gliomas. Am J Pathol. 1997;150:2143–2152. [PMC free article] [PubMed] [Google Scholar]
  • [32].Murayama K., Kobayashi T., Imaizumi T., Matsunaga K., Kuramoto T., Shigemori M., et al. Expression of the SART3 tumor-rejection antigen in brain tumors and induction of cytotoxic T lymphocytes by its peptides. J Immunother. 2000;23:511–518. doi: 10.1097/00002371-200009000-00001. [DOI] [PubMed] [Google Scholar]
  • [33].Liu F.S., Wang Z.C., Li J.H., Lin S., Ren M., Xiao Q., et al. Experimental study of bone-marrow-derived dendritic cells pulsed with tumor antigens in the treatment for intracranial gliomas. Chin J Neurosurg. 2002;18:91–95. [Google Scholar]
  • [34].Jiao B., Li C., Zhang Q., Bai B., Geng S. In vitro experiment research of the antiglioma activity of the glioma vaccine made from dendritic cell. Chin J Neurosurg Dis Res. 2005;4:486–491. [Google Scholar]
  • [35].Kikuchi T., Akasaki Y., Abe T., Fukuda T., Saotome H., Ryan J.L., et al. Vaccination of gliom a patients with fusions of dendritic and glioma cells and recombinant human interleukin-12. J Immunother. 2004;27:452–459. doi: 10.1097/00002371-200411000-00005. [DOI] [PubMed] [Google Scholar]
  • [36].Eggert A.A., Schreurs M.W., Boerman O.C., Oyen W.J., de Boer A.J., Punt C.J., et al. Biodistribution and vaccine efficiency of murine dendritic cells are dependent on the route of administration. Cancer Res. 1999;59:3340–3345. [PubMed] [Google Scholar]
  • [37].Ali S., Curtin J.F., Zirger J.M., Xiong W., King G.D., Barcia C., et al. Inflammatory and anti-glioma effects of an adenovirus expressing human soluble Fms-like tyrosine kinase 3 ligand (hsFlt3L): treatment with hsFlt3L inhibits intracranial glioma progression. Mol Ther. 2004;10:1071–1084. doi: 10.1016/j.ymthe.2004.08.025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [38].Dhodapkar M.V., Krasovsky J., Steinman R.M., Bhardwaj N. Mature dendritic cells boost functionally superior CD8+ T-cell in humans without foreign helper epitopes. J Clin Invest. 2000;105:R9–R14. doi: 10.1172/JCI9051. [DOI] [PMC free article] [PubMed] [Google Scholar]

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