Immunologic Considerations of Patients with Brain Tumors

  • M. S. MahaleyJr.
  • G. Yancey Gillespie
Part of the Cancer Treatment and Research book series (CTAR, volume 12)


Continued interest in the immunologic considerations of patients with malignant gliomas stems from the frustration that clinicians face in current concepts of management coupled with the attractiveness of the hypothetical, selective destruction of malignant cells by elements of the immune system. Our frustration with current therapies is exemplified by the fact that the most effective combinations of surgery, radiotherapy, and chemotherapy for malignant gliomas only increases the median survival time from 17 weeks for patients untreated postoperatively to a little over a year for optimally treated patients [1]. The attractiveness of mobilizing the immune system to control neoplasia has undoubtedly been promoted by the recognized cellular immune responses that all too successfully result in transplantation rejections together with the humoral (antibody) immune mechanisms responsible for specific and timely neutralization and destruction of microbial invaders.


Brain Tumor Glioma Cell Malignant Glioma Glioma Patient Brain Tumor Patient 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Walker MD, Green SB, Byar DP, Alexander E Jr, Batzdorf U, Brooks WH, Hunt WE, MacCarty CS, Mahaley MS Jr, Mealey J Jr, Owens G, Ransohoff J II, Robertson JT, Shapiro WR, Smith KR Jr, Wilson CB, Strike TA:Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Eng J Med 303:1323–1329, 1980.CrossRefGoogle Scholar
  2. 2.
    Bigner DD, Bigner SH, Ponten J, Westermark B, Mahaley MS Jr, Ruoslahti E, Herschman H, Eng LF, Wikstrand CJ:Heterogeneity of genotypic and phenotypic characteristics of fifteen permanent cell lines derived from human gliomas. J Neuropath Exp Neurol 40 (3):201–229, 1981.PubMedCrossRefGoogle Scholar
  3. 3.
    Bullard DE, Bigner SH, Bigner DD:The morphologic response of cell lines derived from human gliomas to dibutyryl adenosine 3’:5’-cyclic monophosphate. J Neuropath Exp Neurol 49 (2):230–246, 1981.CrossRefGoogle Scholar
  4. 4.
    Burger PC, Mahaley MS Jr, Dudka L, Vogel FS:The morphologic effects of radiation administered therapeutically for intracranial gliomas. Cancer 44:1256–1272, 1979.PubMedCrossRefGoogle Scholar
  5. 5.
    Aronin PA, Mahaley MS Jr, Rudnick SA, Dudka L, Donohue J, Selker R, Moore P:Predicting BCNU pulmonary toxicity in patients with malignant gliomas. An assessment of risk factors. N Eng J Med 303:183–188, 1980.CrossRefGoogle Scholar
  6. 6.
    Brooks WH, Netsky MG, Normansell DE, Horowitz DA:Depressed cell-mediated immunity in patients with primary intracranial tumors. J Exp Med 136:1631–1647, 1972.PubMedCrossRefGoogle Scholar
  7. 7.
    Brooks WH, Caldwell HD, Mortara RH:Immune responses in patients with gliomas. Surg Neurol 2:419–423, 1974.PubMedGoogle Scholar
  8. 8.
    Mahaley MS Jr, Brooks WH, Roszman TL, Bigner DD, Dudka L, Richardson S:Immunobiology of primary intracranial tumors. I. Studies of the cellular and humoral general immune competence of brain tumor patients. J Neurosurg 46:467–476, 1977.PubMedCrossRefGoogle Scholar
  9. 9.
    Thomas DGT, Lannigan CB, Behan PO:Impaired cell-mediated immunity in human brain tumours. Lancet 1:1389, 1975.PubMedCrossRefGoogle Scholar
  10. 10.
    Young HF, Sakalas R, Kaplan AM:Inhibition of cell-mediated immunity in patients with brain tumor. Surg Neurol 5:19–23, 1976.PubMedGoogle Scholar
  11. 11.
    Brooks WH, Roszman TL, Rogers AS:Impairment of rosette-forming T lymphocytes in patients with primary intracranial neoplasms. Cancer 37:1869–1873, 1976.PubMedCrossRefGoogle Scholar
  12. 12.
    Brooks WH, Latta RB, Mahaley MS, Roszman TL, Dudka L, Skaggs C:Immunobiology of primary intracranial tumors. Part 5:Correlation of a lymphocyte index and clinical status. J Neurosurg 54:331–337, 1981.PubMedCrossRefGoogle Scholar
  13. 13.
    Roszman TL, Brooks WH, Elliott LH:Immunobiology of primary intracranial tumors. VI. Suppressor cell function and lectin-binding lymphocyte subpopulations in patients with cerebral tumors. Cancer:In press, 1981.Google Scholar
  14. 14.
    Braun DP, Penn RD, Flannery AM, Harris JE:Immunoregulatory cell function in peripheral blood leukocytes of brain cancer patients. Personal communication of a preprint.Google Scholar
  15. 15.
    Weiss JF, Morantz RA, Bradley WP, Chretien PB:Serum acute-phase proteins and immunoglobulins in patients with gliomas. Cancer Res 39:542–544, 1979.PubMedGoogle Scholar
  16. 16.
    Tokumaru T, Catalano LW:Elevation of serum immunoglobulin M(IgM) level in patients with brain tumors. Surg Neurol 4:17–21, 1975.PubMedGoogle Scholar
  17. 17.
    Brooks WH, Roszman TL, Mahaley MS, Woosley RE:Immunobiology of primary intracranial tumours. II. Analysis of lymphocyte subpopulations in patients with primary brain tumours. Clin Exp Immunol 29:61–66, 1977.PubMedGoogle Scholar
  18. 18.
    Woosley RE, Mahaley MS Jr, Mahaley JL, Miller GM, Brooks WH:Immunobiology of primary intracranial tumors. 3. Microcytotoxicity assays of specific immune responses of brain tumors patients. J Neurosurg 47:871–885, 1977.PubMedCrossRefGoogle Scholar
  19. 19.
    deTribolet N, Martin-Achard A, Louis JA:Circulating immune complexes in patients with gliomas. Acta Neurochir (Suppl) 28:437–474, 1979.Google Scholar
  20. 20.
    Martin-Achard A, de Tribolet N, Louis JA, Zander E:Immune complexes associated with brain tumors:Correlation with prognosis. Surg Neurol 13:161–163, 1980.PubMedGoogle Scholar
  21. 21.
    Heier HE, Carpentier N, Lange G, Lambert PH, Godel T:Circulating immune complexes in patients with malignant lymphomas and solid tumors. Int J Cancer 20:887–894, 1977.PubMedCrossRefGoogle Scholar
  22. 22.
    Ridley A, Cavanagh JB:Lymphocytic infiltration in gliomas:Evidence of possible host resistance. Brain 94:117–124, 1971.PubMedCrossRefGoogle Scholar
  23. 23.
    Takeuchi J, Barnard RO:Perivascular lymphocytic cuffing in astrocytomas. Acta Neuropath (Berl) 35:265–271, 1976.PubMedGoogle Scholar
  24. 24.
    DiLorenzo N, Palma L, Nicole S:Lymphocytic infiltration in long-survival glioblastoma:Possible host’s resistance. Acta Neurochir 39:27–33, 1977.CrossRefGoogle Scholar
  25. 25.
    Palma L, DiLorenzo N, Guidetti B:Lymphocytic infiltrates in primary glioblastomas and recidivous gliomas. J Neurosurg 49:854–861, 1978.PubMedCrossRefGoogle Scholar
  26. 26.
    Brooks WH, Markesbery WR, Gupta GD, Roszman TL:Relationship of lymphocyte invasion and survival of brain tumor patients. Ann Neurol 4:219–224, 1978.PubMedCrossRefGoogle Scholar
  27. 27.
    Stavrou D, Anzil AP, Weidenbach W, Rodt H:Immunofluorescence study of lymphocytic in-filtration in gliomas. Identification of T lymphocytes. J Neurol Sei 33:275–282, 1977.CrossRefGoogle Scholar
  28. 28.
    Wood GW, Morantz RA:Immunohistologic evaluation of the lymphoreticular infiltrate of human central nervous system tumors. J Natl Cancer Inst 62:485–491, 1979.PubMedGoogle Scholar
  29. 29.
    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 50:305–311, 1979.PubMedCrossRefGoogle Scholar
  30. 30.
    Synderman R, Pike MC:Pathophysiological aspects of leukocyte Chemotaxis:Identification of a specific chemotactic factor binding site on human granulocytes and defects of macrophage function associated with neoplasia. In:Leukocyte Chemotaxis:Methods physiology and clinical implications, Gallin JI, Quie PG (eds), New York, Raven Press, 1978, p 357.Google Scholar
  31. 31.
    Kay NE, Murray KJ, Douglas SD:Neutrophil Chemotaxis in cerebral astrocytoma. Surg Neurol 8:255–257, 1977.PubMedGoogle Scholar
  32. 32.
    Tabuchi K, Kirsch WM:Detection of IgG on glioblastoma cell surface in vivo. Acta Neurochir 43:93–100, 1978.CrossRefGoogle Scholar
  33. 33.
    Wood GW, Morantz RA, Tilzer SA, Gollahon KA:Immunoglobulin bound in vivo to Fc receptor-positive cells in human central nervous system tumors. J Natl Cancer Inst 64:411–418, 1980.PubMedGoogle Scholar
  34. 34.
    Aarli JA, Aparicio SR, Lumsden CE, Tonder O:Binding of normal human IgG to myelin sheaths, glia and neurons. Immunology 28:171–185, 1975.PubMedGoogle Scholar
  35. 35.
    Ciembroniewicz J, Kolar O:Tissue culture studies of glioblastoma multiforme. Acta Cytol 13:42–49, 1969.PubMedGoogle Scholar
  36. 36.
    Egger AE:Autoradiographic and fluorescence antibody studies of the human host immune response to gliomas. Neurology (Minneap) 22:246–250, 1972.Google Scholar
  37. 37.
    Sheikh KM A, Apuzzo ML J, Weiss MH:Specific cellular immune responses in patients with malignant gliomas. Cancer Res 39:1733–1738, 1979.PubMedGoogle Scholar
  38. 38.
    Apuzzo ML J, Sheikh KM A, Weiss MH, Heiden JS, Kurze T:The utilization of native glioma antigens in the assessment of specific cellular and humoral immune responses in malignant glioma patients. Acta Neurochir 55:180–200, 1981.CrossRefGoogle Scholar
  39. 39.
    Kumar S, Taylor G, Steward JK, Waghe MA, Morris-Jones P:Cell-mediated immunity and blocking factors in patients with tumours of the central nervous system. Int J Cancer 12:194–205, 1973.PubMedCrossRefGoogle Scholar
  40. 40.
    Kornblith PL, Dohan FC, Wood W, Whitman BO:Human astrocytomas:Serum-mediated immunologic response. Cancer 33:1512–1519, 1974.PubMedCrossRefGoogle Scholar
  41. 41.
    Quindlen EA, Dohan FC, Kornblith PL:Improved assay for cytotoxic antiglioma antibody. Surg Forum 25:464–466, 1974.PubMedGoogle Scholar
  42. 42.
    Martin-Achard A, Diserens A-C, de Tribolet N, Carrel S:Evaluation of the humoral response of glioma patients to a possible common tumor-associated antigen(s). Int J Cancer 25:219–224, 1980.PubMedCrossRefGoogle Scholar
  43. 43.
    Coakham HB, Kornblith PL:The humoral immune response of patients to their gliomas. Acta Neurochir (Suppl) 28:475–479, 1979.Google Scholar
  44. 44.
    Coakham HB, Kornblith PL, Quindlen EA, Pollock LA, Wood WC, Hartnett LC:Autologous humoral response to human gliomas and analysis of certain cell surface antigens:In vitro study with the use of microcytotoxicity and immune adherence assyas. J Natl Cancer Inst 64 (2):223–233, 1980.PubMedGoogle Scholar
  45. 45.
    DeCarvalho S, Kaufman A, Pineda A:Adjuvant chemo-immunotherapy in central nervous system tumors. In:Adjuvant therapy of cancer, Salmon SE, Josen SE (eds), Amsterdam:Elsevier/North Holland Biomedical Press, 1977, pp 495–502.Google Scholar
  46. 46.
    Selker RG, Wolmark N, Fisher B, Moore P:Preliminary observations on the use of Coryne- bacterium parvum in patients with primary intracranial tumors:Effect on intracranial pressure. J Surg Oncol 10:299–303, 1978.PubMedCrossRefGoogle Scholar
  47. 47.
    Mahaley MS Jr, Steinbok P, Aronin P, Dudka L, Zinn D:Immunobiology of primary intracranial tumors. V. Levamisole as an immune stimulant in patients and in the ASV glioma model. J Neurosurg 54:220–227, 1981.PubMedCrossRefGoogle Scholar
  48. 48.
    Ommaya AK, Reed J, Walters CL, Meeker WR, Weiss JF:Thymosin for brain tumor therapy. A phase I trial in patients with malignant gliomas. In:Abstracts of the AANS Meeting. ( Poster Section ), 1981, p 90.Google Scholar
  49. 49.
    Trouillas P, Lapras CL:Immunotherapie active des tumeurs cerebrales. Neuro-Chirurgie 16:143–170, 1970.PubMedGoogle Scholar
  50. 50.
    Takakura K, Miki Y, Kubo O, Ogawa N, Matsutani M, Sano K:Adjuvant immunotherapy for malignant brain tumors. Jap J Clin Oncol 12:109–120, 1972.Google Scholar
  51. 51.
    Young HF, Kaplan AM, Regelson W:Immunotherapy with autologous white cell infusions (‘lymphocytes’) in the treatment of recurrent glioblastoma multiforme. Cancer 40:1037–1044, 1977PubMedCrossRefGoogle Scholar
  52. 52.
    Neuwelt EA, Clark K, Kirkpatrick JB, Toben H:Clinical studies of intrathecal autologous lymphocyte infusions in patients with malignant gliomas:A toxicity study. Ann Neurol 4:307–312, 1978PubMedCrossRefGoogle Scholar
  53. 53.
    Roda JE, Heredero J J, Villarejo F J, Roda JM:Tumoural antigens on experimental and human glioblastoma. Acta Neurochir 53:187–204, 1980.CrossRefGoogle Scholar
  54. 54.
    Garson JA, Quindlen EA, Kornblith PL:Complement fixation by IgM and IgG autoantibodies on cultured human glial cells. J Neurosurg 55:19–26, 1981.PubMedCrossRefGoogle Scholar
  55. 55.
    Mahaley MS Jr, Mahaley JL, Day ED:The localization of radio-antibodies in human brain tumors. II. Radioautography. Cancer Res 25:779–793, 1965.Google Scholar
  56. 56.
    Kennett RH, Gilbert FM:Hybrid myelomas producing antibodies against a human neuro-blastoma antigen present on fetal brain. Science 203:1120–1121, 1978.CrossRefGoogle Scholar
  57. 57.
    Carrel S, Accolla RS, Carmagnola AL, Mach J-P:Demonstration of human melanoma associated antigen(s) by monoclonal antibodies. In:Protides of biological fluids, Peeters H (ed), vol 27, Oxford, Pergamon Press, 1980, pp 505–509.Google Scholar
  58. 58.
    Herlyn M, Clark WH Jr, Mastrangelo MJ, Guerry D IV, Elder D, La Rossa O, Hamilton R, Bondi E, Tuthill R, Steplewski Z, Koprowski H:Specific reactivity of monoclonal anti-melanoma antibodies. Cancer Res 40:3602–3609, 1980.PubMedGoogle Scholar
  59. 59.
    Imai K, Ng A-K, Ferrone S:Characterization of monoclonal antibodies to human melanoma- associated antigens. J Nat Cancer Inst 66 (3):489–496, 1981.PubMedGoogle Scholar
  60. 60.
    Schnegg JF, Diserens AC, Carrel S, Accolla RS, de Tribolet N:Human glioma-associated antigens detected by monoclonal antibodies. Cancer Res 41:1209–1213, 1981.PubMedGoogle Scholar
  61. 61.
    Seeger RC, Rosenblatt HM, Imai K, Ferrone S:Common antigenic determinants on human melanoma, glioma, neuroblastoma and sarcoma cells defined with monoclonal antibodies. Cancer Res 41:2714–2717, 1981.PubMedGoogle Scholar
  62. 62.
    Bourdon MA, Wikstrand CJ, Pegram CN, Bigner DD:A glioma-mesenchymal extracellular matrix (GMEM) antigen defined by monoclonal antibody. Fed Proc 40:821 (Abstract 3358), 1981.Google Scholar
  63. 63.
    Bloom WH, Carstaris KC, Crompton MR, McKissock W:Autologous glioma transplantation. Lancet 2:77–78, 1960.PubMedCrossRefGoogle Scholar
  64. 64.
    Grace JT Jr, Perese DM, Metzgar RS, Sasabe T, Holdridge B:Tumor autograft responses in patients with glioblastoma multiforme. J Neurosurg 18:159–167, 1961.CrossRefGoogle Scholar
  65. 65.
    Trouillas P:Immunologic et immunotherapie des tumeurs cerebrales. Neurologique 128:23–34, 1973.Google Scholar
  66. 66.
    Febvre H, Maunoury R, Constans JP, Trouillas P:Reactions d’hypersensibilite retardee avec des lignees de cellules tumorales cultivees in vitro chez des malades porteurs de tumeurs cerebrales malignes. Int J Cancer 10:221–232, 1972.PubMedCrossRefGoogle Scholar
  67. 67.
    Bloom HJ, Peckham MJ, Richardson AE, Alexander PA, Payne PM:Glioblastoma multiforme:A controlled trial to assess the value of specific active immunotherapy in patients treated by radical surgery and radiotherapy. Brit J Cancer 27:253–267, 1973.PubMedCrossRefGoogle Scholar
  68. 68.
    Bigner DD, Pitts OM, Wikstrand CJ:Induction of lethal experimental allergic encephalomyelitis in nonhuman primates and guinea pigs with human glioblastoma multiforme tissue. J Neurosurg 55:32–42, 1981.PubMedCrossRefGoogle Scholar
  69. 69.
    Gillespie RP, Mahaley MS Jr, Gillespie GY:Unpublished observations.Google Scholar
  70. 70.
    Kerbel RS, Blakeslee D:Rapid adsorption of a foetal calf serum component by mammalian cells in culture. A potential source of artefacts in studies of antisera to cell-specific antigens. Immunology 31:881–891, 1976.PubMedGoogle Scholar
  71. 71.
    Grimson BS, Mahaley MS Jr, Dubey HD, Dudka L:Ophthalmic and central nervous system complications following intra-carotid BCNU (Carmustine). Accepted for publication. J Clin Neuroophthal, 1981.Google Scholar
  72. 71.
    Stavrou D, Hulten M, Anzil AP, Bilzer T:The humoral antibody response of rats immunized with chemically modified syngeneic brain cells and glioma cells. Int J Cancer 26:629–637, 1980.PubMedCrossRefGoogle Scholar
  73. 73.
    Maruyama Y:Dose-dependent recognition of irradiated isogeneic mouse lymphoma cells:Study by terminal dilution assay. Int J Cancer 3:593–602, 1968.PubMedCrossRefGoogle Scholar
  74. 74.
    Sato I, Nio Y, Abe M:In vitro production of an anti-tumor agent by reticuloendothelial cells. Gann 59:273–280, 1968.PubMedGoogle Scholar

Copyright information

© Martinus Nijhoff Publishers, Boston/The Hague/Dordrecht/Lancaster 1983

Authors and Affiliations

  • M. S. MahaleyJr.
  • G. Yancey Gillespie

There are no affiliations available

Personalised recommendations