Child's Nervous System

, Volume 5, Issue 2, pp 60–65 | Cite as

Immunology of gliomas

  • Nicolas de Tribolet
Review Paper


The treatment of cerebral gliomas continues to challenge neurosurgeons and research scientists. The lack of major success with chemotherapy and radiation therapy has given rise to further investigation into the biology of these tumors and host reactions to them. Much of this research has centered upon the evaluation of tumor cell antigenicity and on both the humoral and cellular immune responses to gliomas. Contrary to previous considerations, evidence suggests that astrocytes, glioma cells, and tumor endothelial cells may all have pivotal roles in the initiation and prolongation of both local and systemic immune responses to the tumor. In this review we will discuss the immunobiology of the glioma with specific reference to the interactions between the tumor and the host immune system. In addition, ideas for potential therapeutic manipulation of the host-glioma immune interactions will be reviewed, stressing potential pitfalls and risks.

Key words

Glioma Lymphokines HLA Lymphocytes Immunobiology 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Apuzzo MLJ, Mitchell MS (1981) Immunological aspects of intrinsic glial tumors. J Neurosurg 55:1–18Google Scholar
  2. 2.
    Basu A, Murthy U, Rodeck U, Herlyn M, Mattes L, Das M (1987) Presence of tumor-associated antigens in epidermal growth factor receptors from different human carcinomas. Cancer Res 47:2531–2536Google Scholar
  3. 3.
    Behnke J, Mach JP, Buchegger F, Carrel S, Delaloye B, de Tribolet N (1988) In vivo localisation of radiolabelled monoclonal antibody in human gliomas. Br J Neurosurg 2:193–197Google Scholar
  4. 4.
    Bigner DD (1982) The biology of gliomas: potential clinical implications of glioma cellular heterogeneity. Neurosurgery 9:320–326Google Scholar
  5. 5.
    Cairncross J, Mattes MJ, Beresford HR, Albino AP, Houghton AN, Lloyd KO, Old LJ (1982) Cell surface antigens of human astrocytoma defined by mouse monoclonal antibodies: identification of astrocytoma subsets. Proc Natl Acad Sci USA 79:5641–5645Google Scholar
  6. 6.
    Carrel S, de Tribolet N, Mach JP (1982) Expression of neuroectodermal antigens common to melanomas, gliomas and neuroblastomas. Acta Neuropathol 57:158–164Google Scholar
  7. 7.
    Carrel S, de Tribolet N, Gross N (1982) Expression of HLADR and common acute lymphoblastic leukemia antigens on glioma cells. Eur J Immunol 12:354–357Google Scholar
  8. 8.
    Coakham HB (1984) Immunology of human brain tumors. Eur J Cancer Clin Oncol 20:145–149Google Scholar
  9. 9.
    Coakham HB, Lakshmi MS (1975) Tumor associated surface antigens in human astrocytomas. Oncology 31:223–243Google Scholar
  10. 10.
    Coakham HB, Garson JA, Brownwell B, Kemshead JT (1984) Monoclonal antibodies as reagents for brain tumor diagnosis, a review. J R Soc Med 77:780–787Google Scholar
  11. 11.
    Coakham HB, Garson JA, Allan PA, Harper EI, Brownell B, Kemshead JT, Lane EB (1985) Immunohistological diagnosis of central nervous system tumors using a monoclonal antibody panel. J Clin Pathol 38:165–173Google Scholar
  12. 12.
    Coakham HB, Richardson RB, Davies AG, Bourne SP, Eckert H, Kemshead JT (1988) Neoplastic meningitis from a pineal tumour treated by antibody-guided irradiation via the intrathecal route. Br J Neurosurg 2:199–209Google Scholar
  13. 13.
    De Muralt B, de Tribolet N, Diserens AC, Carrel S, Mach JP (1983) Reactivity of antiglioma monoclonal antibodies for a large planel of cultured gliomas and other neuroectodermal derived tumors. Anticancer Res 3:1–6Google Scholar
  14. 14.
    De Martin R, Haendler B, Hofer-Warbinek R, Gaugitsch H, Wrann M, Schlusener H, Seifert JM, Bodmer S, Fontana A, Hofer E (1987) Complementary DNA for human glioblastoma-derived T cell suppressor factor, a novel member of the transforming growth factor-B gene family. EMBO J 6:3673–3677Google Scholar
  15. 15.
    De Tribolet N, Carrel S (1980) Human glioma-associated antigens. Cancer Immunol Immunother 9:207Google Scholar
  16. 16.
    De Tribolet N, Carrel S, Mach JP (1984) Brain tumor associated antigens. Prog Exp Tumor Res 27:118–131Google Scholar
  17. 17.
    Dickinson JG, Flanigan TP, Kemshead JT, Doherty D, Walsh FS (1983) Identification of cell surface antigens present exclusively on a sub-population of astrocytes in human foetal brain cultures. J Neuroimmunol 5:111–123Google Scholar
  18. 18.
    Fontana A, Fierz W, Wekerle H (1984) Astrocytes present myelin basic protein to encephalitogenic T cell lines. Nature 307:273–276Google Scholar
  19. 19.
    Fontana A, Hengartner H, de Tribolet N, Weber E (1984) Glioblastoma cells release both Interleukin 1 and factors inhibiting Interleukin 2 mediated effects. J Immunol 132:1837–1844Google Scholar
  20. 20.
    Gately MK, Glaser M, Dick SJ, Meitetal RW, Kornblith PL (1982) In vitro studies on the cell-mediated immune response to human brain tumors. I. Requirement of third party stimulator lymphocytes in the induction of cell mediated cytotoxic responses to allogeneic cultures of gliomas. JNCI 69:1245–1254Google Scholar
  21. 21.
    Gerosa M, Chilosi M, Iannucci A, Montagna M, Andrighetto GC, Stevanoni G, Tridente G (1984) Immunohistochemical characterization of Ia-DR positive cells in normal brain and gliomas. J Neurol Oncol 2:272Google Scholar
  22. 22.
    Hunter T (1984) The epidermal growth factor gene and its products. Nature 311:414–416Google Scholar
  23. 23.
    Jacobs SK, Wilson DJ, Kornblith PL, Grimm EA (1986) Interleukin-2 or autologous lymphokine-activated killer cell treatment of malignant glioma: phase 1 trial. Cancer Res 46:2101–2104Google Scholar
  24. 24.
    Kemshead JT, Ritter MA, Cotmore SF, Greaves MF (1982) Human Thy-1 expression on cell surfaces of neuronal and glial cells. Brain Res 236:451–461Google Scholar
  25. 25.
    Kennett RH, Gilbert FM (1978) Hybrid melanomas producing antibodies against human neuroblastoma antigen present on foetal brain. Science 203:1120–1121Google Scholar
  26. 26.
    Köhler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497Google Scholar
  27. 27.
    Kornblith PL, Dohan FC Jr, Wood WC, Whitman BO (1974) Human astrocytoma: serum-mediated immunologic response. Cancer 33:1512–1519Google Scholar
  28. 28.
    Kuppner MC, Hamou MF, Bodmer S, Fontana A, Tribolet N de (1988) The glioblastoma-derived T cell suppressor factor/transforming growth factor B2 inhibits the generation of lymphokine activated killer (LAK) cells. Int J Cancer 42:562–567Google Scholar
  29. 29.
    Libermann TA, Nussbaum HR, Razon N (1985) Amplification, enhanced expression and possible rearrangement of EGFR gene in human brain tumors. Nature 313:144–146Google Scholar
  30. 30.
    Mahaley MS Jr (1972) Experiences with antibody production from human glioma tissue. Prog Exp Tumor Res 17:31–39Google Scholar
  31. 31.
    Martin-Achard A, Diserens AC, Tribolet N de, Carrel S (1980) Evaluation of the humoral response of glioma patients to a possible common tumor-associated antigen(s). Int J Cancer 25:219–224Google Scholar
  32. 32.
    Miescher S, Whiteside TL, Tribolet N de, von Fliedner V (1988) In situ characterization, clonogenic potential and antitumor cytolytic activity of T lymphocytes infiltrating human brain cancers. J Neurosurg 68:438–448Google Scholar
  33. 33.
    Neuwelt EA (1984) Therapeutic potential for blood brain barrier modification in malignant brain tumors. Prog Exp Tumor Res 28:51–66Google Scholar
  34. 34.
    Pfreundschuh M, Shiku H, Takahashi Tueda R, Ransohoff J, Oettgen HF, Old L (1978) Serologic analysis of cell surface antigens of malignant human brain tumors. Proc Natl Acad Sci USA 75:5122–5126Google Scholar
  35. 35.
    Pfreundschuh M, Röhrich M, Piotrowski W, Berlit P, Penzholz H (1982) Natural antibodies to cell surface antigens of human astrocytoma. Int J Cancer 29:517–521Google Scholar
  36. 36.
    Piguet V, Diserens AC, Carrel S, Mach JP, Tribolet N de (1985) The immunology of human gliomas. Springer Semin Immunopathol 8:111–127Google Scholar
  37. 37.
    Piguet V, Carrel S, Diserens AC, Mach JP, Tribolet N de (1986) Heterogeneity of the induction of HLA-DR expression by IFN Gamma on glioma cell lines and their clones. JNCI 76:223–227Google Scholar
  38. 38.
    Rodeck U, Herlyn M, Koprowski H (1987) Interaction between growth factor receptors and corresponding monoclonal antibodies in human tumors. J Cell Biochem 35:315–320Google Scholar
  39. 39.
    Roszman TL, Brooks WM, Elliott LH (1982) Immunology of primary intracranial tumors. VI. Suppressor cell functional lectin binding lymphocyte subpopulations in patients with cerebral tumors. Cancer 50:1273–1279Google Scholar
  40. 40.
    Schnegg JF, Tribolet N de, Diserens AC, Martin-Achard A, Carrel S (1981) Characterization of a rabbit antihuman malignant glioma antiserum. J Cancer 28:265–269Google Scholar
  41. 41.
    Schreyer M, Hamou MF, Carrel S, Mach JP, Tribolet N de (1986) Immunohistological localization of glioma and melanoma associated antigens with monoclonal antibodies. In: Stoal GEJ, Van Veelen CWM (eds) Markers of human neuroectodermal tumors. CRC Press, Boca Raton, Florida, pp 53–62Google Scholar
  42. 42.
    Seeger RC, Rosenblatt HM, Imai K, Ferrone S (1981) Common antigenic determinants of human melanoma, glioma, neuroblastoma and sarcoma cells defined by monoclonal antibodies. Cancer Res 41:2712–2717Google Scholar
  43. 43.
    Seeger RC, Damon YL, Rayner SA, Hoover F (1982) Definition of Thy-1 determinant of human neuroblastoma, glioma, sarcoma and teratoma cells with monoclonal antibody. J Immunol 128:983–989Google Scholar
  44. 44.
    Shapiro JR, Yung WA, Shapiro WR (1981) Isolation, karyotype and clonal growth of heterogeneous subpopulations of human malignant gliomas. Cancer Res 41:23–59Google Scholar
  45. 45.
    Sjögren HO, Hellstrom I, Bansal SC (1971) Suggestive evidence that “blocking antibodies” of tumor-bearing individuals may be antigen-antibody complexes. Proc Natl Acad Sci USA 68:1372–1375Google Scholar
  46. 46.
    Tabuchi K, Kirsch WM (1978) Detection of IgG on glioblastoma cell surface in vivo. Acta Neurochir 43:93–100Google Scholar
  47. 47.
    Thomas DGT, Lannigan CB, Behman PO (1975) Impaired cell mediated immunity in human brain tumors. Lancet I:1389–1392Google Scholar
  48. 48.
    Unanue ER, Beller DI, Lu CY, Allen PM (1984) Antigen presentation: Comments on its regulation and mechanisms. J Immunol 132:1–14Google Scholar
  49. 49.
    Von Hanwehr RI, Hofman FM, Taylor CR, Apuzzo MLJ (1984) Mononuclear lymphoid populations infiltrating the microenvironment of primary CNS tumors. J Neurosurg 60:1138–1147Google Scholar
  50. 50.
    Wikstrand CJ, Bigner SH, Bigner DD (1983) Demonstration of complex antigenic heterogeneity in a human glioma cell line and eight derived clones by specific monoclonal antibodies. Cancer Res 43:3327–3334Google Scholar
  51. 51.
    Wikstrand CJ, Mahaley MS, Bigner DD (1977) Surface antigenic characteristics of human glial brain tumors. Cancer Res 37:4267–4275Google Scholar
  52. 52.
    Yamasaki T, Yamasaki J, Wanda H, Watanabe Y, Naba Y, Hanadka M (1984) Specific adoptive immunotherapy with tumor specific cytotoxic T lymphocyte clone for murine malignant gliomas. Cancer Res 44:1776–1783Google Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • Nicolas de Tribolet
    • 1
  1. 1.Department of NeurosurgeryUniversity HospitalLausanneSwitzerland

Personalised recommendations