Acta Neurochirurgica

, Volume 55, Issue 3–4, pp 181–200 | Cite as

The utilization of native glioma antigens in the assessment of cellular and humoral immune responses in malignant glioma patients

  • M. L. J. Apuzzo
  • K. M. A. Sheikh
  • M. H. Weiss
  • J. S. Heiden
  • T. Kurze


Cellular and humoral components of the immune response have been studied preoperatively, concurrently, and serially in patients with malignant glial neoplasms.

In order to assess titres of circulating antibodies to tumour cell constituents an indirect immunofluorescent technique was applied to single cell suspensions and snap frozen cell smears. In an allogeneic system, 49% of 47 test and 7% of 124 control sera gave a positive response to cytoplasmic components.

The leucocyte adherence inhibition assay was applied to study 39 test and 64 control patients. Significant non-adherence of leukocytes was observed in 77% of test cases. Control parameters indicated specificity of the response.

Simultaneous assessment in 28 test patients yielded a positive response for one or both assays in 89% of cases.


Malignant Glioma Single Cell Suspension Glioma Patient Glial Neoplasm Control Seron 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Table of abbreviations


Peripheral Blood Leucocytes


Leucocyte Adherence Inhibition


Non-Adherence of Leucocytes


Indirect Immunofluorescence


Potassium Chloride


Phosphate Buffered Saline


Minimal Essential Medium


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  1. 1.
    Apuzzo, M. L. J., Sheikh, K. M. A., Tumor Immunology. A neurosurgical perspective. I. General concepts of tumor immunology. Bull. L. A. Neurol. Soc.41 (1976), 168–175.Google Scholar
  2. 2.
    Apuzzo, M. L. J., Tumor Immunology. A neurosurgical perspective. II. The immunology of glial neoplasms. Bull. L. A. Neurol. Soc.41 (1976), 176–183.Google Scholar
  3. 3.
    Apuzzo, M. L. J., Sheikh, K. M. A., Heiden, J. S., Weiss, M. H., Kurze, T., Definition of cellular immune responses to brain antigens in human head trauma. J. Neurosurg.51 (1979), 317–322.PubMedGoogle Scholar
  4. 4.
    Bogoch, S., Astrocytin and malignin: two polypeptide fragments (recognins) related to brain tumor. National Cancer Institute Monograph46 (1976), 133–137.Google Scholar
  5. 5.
    Boker, D.-K., Zur Immunfluoreszenz menschlicher Hirntumoren. Acta neurochir. (Wien)41 (1978), 363–371.Google Scholar
  6. 6.
    Brightman, M. W., Klatzo, I., Olsson, Y., Reese, T. S., The blood-brain barrier to proteins under normal and pathological conditions. J. Neurol. Sci.10 (1970), 215–239.PubMedGoogle Scholar
  7. 7.
    Brooks, W. H., Netsky, M. G., Levine, J. E., Immunity and tumors of the nervous system. Surg. Neurol.3 (1975), 184–186.PubMedGoogle Scholar
  8. 8.
    Brooks, W. H., Netsky, M. G., Normansell, D. E., Horwitz, D. A., Depressed cell-mediated immunity in patients with primary intracranial tumors. J. Exp. Med.136 (1972), 1631–1647.PubMedGoogle Scholar
  9. 9.
    Brooks, W. H., Roszman, T. L., Robers, A. S., Impairment of rosette-forming T lymphocytes in patients with primary intracranial tumors. Cancer37 (1976), 1869–1873.PubMedGoogle Scholar
  10. 10.
    Coakham, H., Surface antigen(s) common to human astrocytoma cells. Nature250 (1974), 328–330.PubMedGoogle Scholar
  11. 11.
    Coakham, H. B., Lakshmi, M. S., Tumor-associated surface antigen(s) in human astrocytomas. Oncol.31 (1975), 233–243.Google Scholar
  12. 12.
    Di Lorenzo, N., Palma, L., Nicole, S., Lymphocytic infiltration in long-survival glioblastomas: possible host's resistance. Acta neurochir. (Wien)39 (1977), 27–33.Google Scholar
  13. 13.
    Dittman, L., Axelsen, N. H., Norgaard-Pedersen, B., Bock, E., Antigens in human glioblastomas and meningiomas: search for tumor and onco-foetal antigen. Estimation of © 100 and GFA protein. Brit. J. Cancer35 (1977), 135–141.PubMedGoogle Scholar
  14. 14.
    Eggers, A. E., Autoradiographic and fluorescence antibody studies on the human host immune response to gliomas. Neurol.22 (1972), 246–250.Google Scholar
  15. 15.
    Flores, M., Marti, J. H., Grosser, N., MacFarlane, J. K., Thompson, D. M. P., An overview: antitumor immunity in breast cancer assayed by tube leukocyte adherence inhibition. Cancer39 (2) (1977), 494–505.PubMedGoogle Scholar
  16. 16.
    Gerosa, M., Amadori, G., Semenzato, C., Raumer, R., Cisotto, P., Pezzuto, A., Gasparotto, G., Carteri, A., Immunobiology of paediatric intracranial tumours. A preliminary report. Acta neurochir. (Wien)50 (1979), 49–54.Google Scholar
  17. 17.
    Grosser, N., Marti, J. H., Proctor, J. W., Thompson, D. M. P., Tube leukocyte adherence inhibition assay for the detection of anti-tumor immunity. I. Monocyte is the reactive cell. Brit. J. Cancer18 (1976), 39–47.Google Scholar
  18. 18.
    Halliday, W. J., Maluish, A., Isbister, W. H., Detection of anti-tumor cell mediated immunity and serum blocking factors in cancer patients by the leukocyte adherence inhibition test. Brit. J. Cancer29 (1974), 31–35.PubMedGoogle Scholar
  19. 19.
    Holt, P. G., Fimmel, P. J., Finlay-Jones, L. M., Flower, R. L., Evaluation of the microplate leukocyte adherence inhibition test and its reproducibility, sensitivity and relationship to other tests of cellular immunity. Cancer Res.39 (1979), 564–569.PubMedGoogle Scholar
  20. 20.
    Kornblith, P. L., Dohan, F. C., Wood, W. C., Whitman, B. S., Human astrocytoma: serum-mediated immunologic response. Cancer33 (1974), 1512–1519.PubMedGoogle Scholar
  21. 21.
    Kornblith, P. L., Prieto, A., Pollen, D. A., Alterations in glial and mesenchymal tumor cell membranes resistance with heteroimmune and autologous sera. Ann. N.Y. Acad. Sci.159 (1969), 585–590.Google Scholar
  22. 22.
    Kumar, P., The biology of human brain tumours. Acta neurochir. (Wien)50 (1979), 7–34.Google Scholar
  23. 23.
    Kumar, S., Taylor, G., Specific lymphocytotoxicity and blocking factors in tumours of the central nervous system. Brit. J. Cancer (Suppl. 1)28 (1973), 135–141.Google Scholar
  24. 24.
    Lach, B., Weinrauder, W., Glia-specific antigen in the intracranial tumors. Immunofluorescence study. Acta neuropath. (Berl.)41 (1978), 9–15.Google Scholar
  25. 25.
    Levy, N., Cell-mediated cytotoxicity and serum-mediated blocking: evidence that their associated determinants on human tumor cells are different. J. Immunol.121 (1978), 916–922.PubMedGoogle Scholar
  26. 26.
    Levy, N. L., Amos, D. B., Solovieff, G. V., dos Reis, A. P., In vitro methods for assessment of antibody-mediated tumor immunity. Natl. Cancer Inst. Monograph35 (1972), 5–11.Google Scholar
  27. 27.
    Levy, N. L., Mahaley jr., M. S., Day, E. D., In vitro demonstration of cell-mediated immunity to human brain tumors. Cancer Res.32 (1972), 477–482.PubMedGoogle Scholar
  28. 28.
    Lewis, M. A., Ikonopisof, R. L., Nairn, R. C., Tumor-specific antibodies in human malignant melanoma and their relationship to the extent of the disease. Brit. J. Med.3 (1969), 547.Google Scholar
  29. 29.
    Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J., Protein measurements with the Folan phenol reagent. J. Biol. Chem.193 (1951), 265–275.PubMedGoogle Scholar
  30. 30.
    Mahaley jr., M. S., Experiences with antibody production from human glioma tissue. Progr. Exp. Tumor Res.17 (1972), 31–39.PubMedGoogle Scholar
  31. 31.
    Mahaley jr., M. S., Immunotherapy of brain tumors. Seminars in Oncology, Vol. 2, No. 1, (1975), 75–78.PubMedGoogle Scholar
  32. 32.
    Mahaley jr., M. S., Brooks, W. H., Roszman, T. L., Bigner, D. D., Dudka, L., Richardson, S., Immunobiology of primary intracranial tumors. Part I: Studies of the cellular and humoral general immune competence of the brain-tumor patients. J. Neurosurg.46 (1977), 467–476.PubMedGoogle Scholar
  33. 33.
    Marti, J. H., Thompson, D. M. P., Anti-tumor immunity in malignant melanoma assay by tube leukocyte adherence inhibition. Brit. J. Cancer34 (1976), 116–133.PubMedGoogle Scholar
  34. 34.
    Martuza, R. L., Shamberger, R. C., Phillips, J. P., Kornblith, P. L., Dohan, F. C., Hochberg, F. H., A lymphocyte-dependent antibody assay for detection of antibodies to human glioma cells. Surg. Forum26 (1975), 492–494.PubMedGoogle Scholar
  35. 35.
    Mavligit, G. M., Gutterman, J. U., Hersh, E. M., Primary brain tumors: tumor immunity and immunocompetence. Surg. Neurol.1 (1973), 261–263.PubMedGoogle Scholar
  36. 36.
    Meltzer, M. S., Leonare, E. J., Rapp, H. J., Borson, T., Tumor specific antigen solubilized by hypertonic potassium chloride. J. Natl. Cancer Inst.47 (1971), 703–709.PubMedGoogle Scholar
  37. 37.
    Mottet, S., Martin-Achard, A., de Tribolet, N., Diserens, A. C., Evaluation of the humoral response of meningioma patients to possible common tumour-associated antigens. Acta neurochir. (Wien)52 (1980), 19–25.Google Scholar
  38. 38.
    Neuwelt, E. A., Garcia, J. H., Kolar, O., Rao, K., Ducker, T., Elevated CSF gamma globulins with cerebral “glioma”. Surg. Neurol.8 (1977), 107–110.PubMedGoogle Scholar
  39. 39.
    Pees, H. W., Cytotoxic immune response of meningioma patients towards allogeneic and autologous tumour cells before and after surgery. Acta neurochir. (Wien)50 (1979), 217–227.Google Scholar
  40. 40.
    Phillips, J. P., Sujatonod, M., Martuza, R. L., Quindlen, E. A., Wood, W. C., Kornblith, P. L., Dohan jr., F. C., Cytotoxic antibodies in preoperative glioma patients: a diagnostic assay. Acta neurochir. (Wien)35 (1976), 43–52.Google Scholar
  41. 41.
    Powell, A., Sloss, A. M., Smith, R. N., Murrwell, H., Antigenic specificity and cellular mechanisms in leukocyte adherence inhibition analysis of immunity to simple proteins and hapten-protein conjugates. Cancer Res.39 (1979), 570–575.PubMedGoogle Scholar
  42. 42.
    Quindlen, E. A., Dohan jr., F. C., Kornblith, P. L., Improved assay for cytotoxic antiglioma antibody. Surg. Forum25 (1974), 464–466.PubMedGoogle Scholar
  43. 43.
    Ridley, A., Neuroimmunology. Immunological aspects of gliomas. Proc. Roy. Soc. Med.70 (1977), 867–869.PubMedGoogle Scholar
  44. 44.
    Roda, J. E., Villarejo, F., Heredero, J., Obrador, S., Heterologous antibodies in human and rat's glioblastoma. Acta neurochir. (Wien)35 (1976), 53–56.Google Scholar
  45. 45.
    Rosner, S., Immunological enhancement of chemotherapy in advanced brain cancer. Acta Neurol. Latinoamer.21 (1975), 126–132.Google Scholar
  46. 46.
    Selker, R. G., Wolmark, N., Fisher, B., Moore, P., Preliminary observations on the use of corynebacterium parvum in patients with primary intracranial tumors: effect on intracranial pressure. J. Surg. Oncol.10 (1978), 299–303.PubMedGoogle Scholar
  47. 47.
    Sheikh, K. M. A., Apuzzo, M. L. J., Kochsiek, K. R., Weiss, M. H., Malignant glial neoplasms: definition of a humoral host response to tumor-associated antigen(s). The Yale J. Biol. and Med.50 (1977), 397–403.Google Scholar
  48. 48.
    Sheikh, K. M. A., Apuzzo, M. L. J., Weiss, M. H., Cellular immune response in malignant gliomas to glioma-associated antigens. Cancer Res.39 (1979), 1729–1734.Google Scholar
  49. 49.
    Sheikh, K. M. A., Brownstein, S., Lewis, M. A., Tumor-specific antibodies in ocular melanoma and their relationship to tumor cell type. Proc. Am. Assoc. Cancer Res. 1975.Google Scholar
  50. 50.
    Solheid, C., Lauor, G., Palladini, G., Two separate membrane bound antigens on human glioma cells in tissue culture detected with sera from glioma patients by immunofluorescence. J. Neurol. Sci.30 (1976), 55–64.PubMedGoogle Scholar
  51. 51.
    Stavrou, D., Anzil, A. P., Weidenbach, W., Rodt, H., Immunofluorescence study of lymphocytic infiltration in gliomas. J. Neurol. Sci.33 (1977), 275–282.PubMedGoogle Scholar
  52. 52.
    Tabuchi, K., Kirsch, W. M., Detection of IgG on glioblastoma cell-surface in vivo. Acta neurochir. (Wien)43 (1978), 93–100.Google Scholar
  53. 53.
    Tabuchi, K., Kirsch, W. M., van Buskirk, J. J., Immunocytochemical evidence for SV 40-related T antigen in two human brain tumours of ependymal origin. Acta neurochir. (Wien)43 (1978), 239–249.Google Scholar
  54. 54.
    Takakura, K., Midi, Y., Kubo, O., Ogawa, N., Matsutani, M., Sano, K., Adjuvant immunotherapy for malignant brain tumors. Jap. J. Clin. Oncol.12 (2) (1972), 109–120.Google Scholar
  55. 55.
    Takasugi, M., Mickey, M. R., Terasaki, P. I., Studies on specificity of cell-mediated immunity in human tumors. J. Natl. Cancer Inst.53 (1974), 1527–1538.PubMedGoogle Scholar
  56. 56.
    Tataryn, D. N., MacFarlane, J. K., Thompson, D. M. P., Leukocyte adherence inhibition for detecting specific tumor immunity in early pancreatic cancer. Lancet1 (2) (1978), 1020–1021.PubMedGoogle Scholar
  57. 57.
    Thomas, D. G. T., Lannigan, C. B., Behan, P. O., Impaired cell-mediated immunity in human brain tumours. Lancet1 (1975), 1389–1390.PubMedGoogle Scholar
  58. 58.
    Thomas, D. G. T., Lannigan, C., Behan, P. O., Impaired lymphocyte protein synthesis in patients with glioma of the brain. Brit. J. Surg.62 (1975), 655.Google Scholar
  59. 59.
    Tokumaru, T., Catalano, L. W., Elevation of serum immunoglobulin M (IgM) level in patients with brain tumors. Surg. Neurol.4 (1975), 17–21.PubMedGoogle Scholar
  60. 60.
    Trachtenberg, M. C., Kornblith, P. L., Hauptli, J., Biophysical properties of cultured human glial cells. Brain Res.38 (1972), 279–298.PubMedGoogle Scholar
  61. 61.
    Trouillas, P., Carcino-fetal antigen in glial tumors. Lancet2 (1971), 552.Google Scholar
  62. 62.
    Wahlstrom, T., Linder, E., Saksela, E., Westermark, B., Tumor specific membrane antigens in established cell lines from gliomas. Cancer34 (1974), 274–279.PubMedGoogle Scholar
  63. 63.
    Wahlstrom, T., Linder, E., Saksela, E., Glia-specific antigens in cell cultures from rabbit brain, human foetal and adult brain, and gliomas. Acta Path. Microbiol. Scand., Sect. B81 (1973), 768–774.Google Scholar
  64. 64.
    Young, H. F., Kaplan, A. M., Cellular immune deficiency in patients with glioblastoma. Surg. Forum26 (62) (1976), 476–478.Google Scholar
  65. 65.
    Young, H. F., Kaplan, A. M., Regelson, W., Immunotherapy with autologous white cell infusions (“lymphocytes”) in the treatment of recurrent glioblastoma multiforme—a preliminary report. Cancer40 (1977), 1037–1044.PubMedGoogle Scholar
  66. 66.
    Young, H. F., Sakalas, R., Kaplan, A. M., Immunologic depression in cerebral gliomas. Adv. Neurol.75 (1976), 327–335.Google Scholar

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • M. L. J. Apuzzo
    • 1
  • K. M. A. Sheikh
    • 1
  • M. H. Weiss
    • 1
  • J. S. Heiden
    • 1
  • T. Kurze
    • 1
  1. 1.Department of Surgery, Division of Neurological SurgeryLos Angeles County/University of Southern California Medical CenterLos AngelesUSA

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